Artykuły w czasopismach na temat „SAPK”
Kliknij ten link, aby zobaczyć inne rodzaje publikacji na ten temat: SAPK.
Utwórz poprawne odniesienie w stylach APA, MLA, Chicago, Harvard i wielu innych
Sprawdź 50 najlepszych artykułów w czasopismach naukowych na temat „SAPK”.
Przycisk „Dodaj do bibliografii” jest dostępny obok każdej pracy w bibliografii. Użyj go – a my automatycznie utworzymy odniesienie bibliograficzne do wybranej pracy w stylu cytowania, którego potrzebujesz: APA, MLA, Harvard, Chicago, Vancouver itp.
Możesz również pobrać pełny tekst publikacji naukowej w formacie „.pdf” i przeczytać adnotację do pracy online, jeśli odpowiednie parametry są dostępne w metadanych.
Przeglądaj artykuły w czasopismach z różnych dziedzin i twórz odpowiednie bibliografie.
1
Schaller, Martin, Matthias Bein, Hans C. Korting, Stefan Baur, Gerald Hamm, Michel Monod, Sabine Beinhauer i Bernhard Hube. "The Secreted Aspartyl Proteinases Sap1 and Sap2 Cause Tissue Damage in an In Vitro Model of Vaginal Candidiasis Based on Reconstituted Human Vaginal Epithelium". Infection and Immunity 71, nr 6 (czerwiec 2003): 3227–34. http://dx.doi.org/10.1128/iai.71.6.3227-3234.2003.
Pełny tekst źródłaStreszczenie:
ABSTRACT Secreted aspartyl proteinases (Saps) contribute to the ability of Candida albicans to cause mucosal and disseminated infections. A model of vaginal candidiasis based on reconstituted human vaginal epithelium (RHVE) was used to study the expression and role of these C. albicans proteinases during infection and tissue damage of vaginal epithelium. Colonization of the RHVE by C. albicans SC5314 did not cause any visible epithelial damage 6 h after inoculation, although expression of SAP2, SAP9, and SAP10 was detected by reverse transcriptase PCR. However, significant epithelial damage was observed after 12 h, concomitant with the additional expression of SAP1, SAP4, and SAP5. Additional transcripts of SAP6 and SAP7 were detected at a later stage of the artificial infection (24 h). Similar SAP expression profiles were observed in three samples isolated from human patients with vaginal candidiasis. In experimental infection, secretion of antigens Sap1 to Sap6 by C. albicans was confirmed at the ultrastructural level by using polyclonal antisera raised against Sap1 to Sap6. Addition of the aspartyl proteinase inhibitors pepstatin A and the human immunodeficiency virus proteinase inhibitors ritonavir and amprenavir strongly reduced the tissue damage of the vaginal epithelia by C. albicans cells. Furthermore, SAP null mutants lacking either SAP1 or SAP2 had a drastically reduced potential to cause tissue damage even though SAP3, SAP4, and SAP7 were up-regulated in these mutants. In contrast the vaginopathic potential of mutants lacking SAP3 or SAP4 to SAP6 was not reduced compared to wild-type cells. These data provide further evidence for a crucial role of Sap1 and Sap2 in C. albicans vaginal infections.
2
Felk, Angelika, Marianne Kretschmar, Antje Albrecht, Martin Schaller, Sabine Beinhauer, Thomas Nichterlein, Dominique Sanglard, Hans C. Korting, Wilhelm Schäfer i Bernhard Hube. "Candida albicans Hyphal Formation and the Expression of the Efg1-Regulated Proteinases Sap4 to Sap6 Are Required for the Invasion of Parenchymal Organs". Infection and Immunity 70, nr 7 (lipiec 2002): 3689–700. http://dx.doi.org/10.1128/iai.70.7.3689-3700.2002.
Pełny tekst źródłaStreszczenie:
ABSTRACT The ability to change between yeast and hyphal cells (dimorphism) is known to be a virulence property of the human pathogen Candida albicans. The pathogenesis of disseminated candidosis involves adhesion and penetration of hyphal cells from a colonized mucosal site to internal organs. Parenchymal organs, such as the liver and pancreas, are invaded by C. albicans wild-type hyphal cells between 4 and 24 h after intraperitoneal (i.p.) infection of mice. In contrast, a hypha-deficient mutant lacking the transcription factor Efg1 was not able to invade or damage these organs. To investigate whether this was due to the inability to undergo the dimorphic transition or due to the lack of hypha-associated factors, we investigated the role of secreted aspartic proteinases during tissue invasion and their association with the different morphologies of C. albicans. Wild-type cells expressed a distinct pattern of SAP genes during i.p. infections. Within the first 72 h after infection, SAP1, SAP2, SAP4, SAP5, SAP6, and SAP9 were the most commonly expressed proteinase genes. Sap1 to Sap3 antigens were found on yeast and hyphal cells, while Sap4 to Sap6 antigens were predominantly found on hyphal cells in close contact with host cells, in particular, eosinophilic leukocytes. Mutants lacking EFG1 had either noticeably reduced or higher expressed levels of SAP4 to SAP6 transcripts in vitro depending on the culture conditions. During infection, efg1 mutants had a strongly reduced ability to produce hyphae, which was associated with reduced levels of SAP4 to SAP6 transcripts. Mutants lacking SAP1 to SAP3 had invasive properties indistinguishable from those of wild-type cells. In contrast, a triple mutant lacking SAP4 to SAP6 showed strongly reduced invasiveness but still produced hyphal cells. When the tissue damage of liver and pancreas caused by single sap4, sap5, and sap6 and double sap4 and -6, sap5 and -6, and sap4 and -5 double mutants was compared to the damage caused by wild-type cells, all mutants which lacked functional SAP6 showed significantly reduced tissue damage. These data demonstrate that strains which produce hyphal cells but lack hypha-associated proteinases, particularly that encoded by SAP6, are less invasive. In addition, it can be concluded that the reduced virulence of hypha-deficient mutants is not only due to the inability to form hyphae but also due to modified expression of the SAP genes normally associated with the hyphal morphology.
3
Tomida, Taichiro, Mutsuhiro Takekawa, Pauline O'Grady i Haruo Saito. "Stimulus-Specific Distinctions in Spatial and Temporal Dynamics of Stress-Activated Protein Kinase Kinase Kinases Revealed by a Fluorescence Resonance Energy Transfer Biosensor". Molecular and Cellular Biology 29, nr 22 (8.09.2009): 6117–27. http://dx.doi.org/10.1128/mcb.00571-09.
Pełny tekst źródłaStreszczenie:
ABSTRACT The stress-activated protein kinases (SAPKs), namely, p38 and JNK, are members of the mitogen-activated protein kinase family and are important determinants of cell fate when cells are exposed to environmental stresses such as UV and osmostress. SAPKs are activated by SAPK kinases (SAP2Ks), which are in turn activated by various SAP2K kinases (SAP3Ks). Because conventional methods, such as immunoblotting using phospho-specific antibodies, measure the average activity of SAP3Ks in a cell population, the intracellular dynamics of SAP3K activity are largely unknown. Here, we developed a reporter of SAP3K activity toward the MKK6 SAP2K, based on fluorescence resonance energy transfer, that can uncover the dynamic behavior of SAP3K activation in cells. Using this reporter, we demonstrated that SAP3K activation occurs either synchronously or asynchronously among a cell population and in different cellular compartments in single cells, depending on the type of stress applied. In particular, SAP3Ks are activated by epidermal growth factor and osmostress on the plasma membrane, by anisomycin and UV in the cytoplasm, and by etoposide in the nucleus. These observations revealed previously unknown heterogeneity in SAPK responses and supplied answers to the question of the cellular location in which various stresses induce stimulus-specific SAPK responses.
4
Naglik, Julian R., George Newport, Theodore C. White, Lynette L. Fernandes-Naglik, John S. Greenspan, Deborah Greenspan, Simon P. Sweet, Stephen J. Challacombe i Nina Agabian. "In Vivo Analysis of Secreted Aspartyl Proteinase Expression in Human Oral Candidiasis". Infection and Immunity 67, nr 5 (1.05.1999): 2482–90. http://dx.doi.org/10.1128/iai.67.5.2482-2490.1999.
Pełny tekst źródłaStreszczenie:
ABSTRACT Secreted aspartyl proteinases are putative virulence factors inCandida infections. Candida albicans possesses at least nine members of a SAP gene family, all of which have been sequenced. Although the expression of the SAPgenes has been extensively characterized under laboratory growth conditions, no studies have analyzed in detail the in vivo expression of these proteinases in human oral colonization and infection. We have developed a reliable and sensitive procedure to detect C. albicans mRNA from whole saliva of patients with oral C. albicans infection and those with asymptomaticCandida carriage. The reverse transcription-PCR protocol was used to determine which of the SAP1 to SAP7genes are expressed by C. albicans during colonization and infection of the oral cavity. SAP2 and the SAP4to SAP6 subfamily were the predominant proteinase genes expressed in the oral cavities of both Candida carriers and patients with oral candidiasis; SAP4, SAP5, orSAP6 mRNA was detected in all subjects. SAP1and SAP3 transcripts were observed only in patients with oral candidiasis. SAP7 mRNA expression, which has never been demonstrated under laboratory conditions, was detected in several of the patient samples. All seven SAP genes were simultaneously expressed in some patients with oral candidiasis. This is the first detailed study showing that the SAP gene family is expressed by C. albicans during colonization and infection in humans and that C. albicans infection is associated with the differential expression of individualSAP genes which may be involved in the pathogenesis of oral candidiasis.
5
Cambien, Béatrice, Manuel Pomeranz, Marie-Ange Millet, Bernard Rossi i Annie Schmid-Alliana. "Signal transduction involved in MCP-1–mediated monocytic transendothelial migration". Blood 97, nr 2 (15.01.2001): 359–66. http://dx.doi.org/10.1182/blood.v97.2.359.
Pełny tekst źródłaStreszczenie:
Abstract Monocyte chemoattractant protein-1 (MCP-1) is a major chemoattractant for monocytes and T lymphocytes. The MonoMac6 cell line was used to examine MCP-1 receptor-mediated signal transduction events in relation to MCP-1–mediated monocytic transendothelial migration. MCP-1 stimulates, with distinct time courses, extracellular signal-related kinases (ERK1 and ERK2) and stress-activated protein kinases (SAPK1/JNK1 and SAPK2/p38). SAPK1/JNK1 activation was blocked by piceatannol, indicating that it is regulated by Syk kinase, whereas SAPK2/p38 activation was inhibited by PP2, revealing an upstream regulation by Src-like kinases. In contrast, ERK activation was insensitive to PP2 and piceatannol. Pertussis toxin, a blocker of Go/Gi proteins, abrogated MCP-1–induced ERK activation, but was without any effect on SAPK1/JNK1 and SAPK2/p38 activation. These results underscore the major implication of Go/Gi proteins and nonreceptor tyrosine kinases in the early MCP-1 signaling. Furthermore, MCP-1–mediated chemotaxis and transendothelial migration were significantly diminished by a high concentration of SB202190, a broad SAPK inhibitor, or by SB203580, a specific inhibitor of SAPK2/p38, and abolished by pertussis toxin treatment. Altogether, these data suggest that coordinated action of distinct signal pathways is required to produce a full response to MCP-1 in terms of monocytic locomotion.
6
ADAM, Dieter, Andrea RUFF, Astrid STRELOW, Katja WIEGMANN i Martin KRÖNKE. "Induction of stress-activated protein kinases/c-Jun N-terminal kinases by the p55 tumour necrosis factor receptor does not require sphingomyelinases". Biochemical Journal 333, nr 2 (15.07.1998): 343–50. http://dx.doi.org/10.1042/bj3330343.
Pełny tekst źródłaStreszczenie:
Ceramide has been implicated in the activation of stress-activated protein kinases/c-Jun N-terminal kinases (SAPK/JNK). Binding of tumour necrosis factor (TNF) to its 55 kDa receptor (TR55) leads to the generation of ceramide through activation of either acid or neutral sphingomyelinase (A/N-SMase) as well as to potent activation of SAPK/JNK. We have examined a putative role of both N- and A-SMase in the TR55-dependent activation of SAPK/JNK. The analysis of TR55 deletion mutants expressed in 70Z/3 pre-B cells revealed that activation of SAPK/JNK occurs independently of N-SMase. Although both SAPK/JNK and A-SMase are activated by the death domain of TR55, pharmacological prevention of the TR55-dependent activation of A-SMase, or proteolytic degradation of A-SMase in 70Z/3 cells, did not impair SAPK/JNK activation, indicating that SAPK/JNK are not secondary to A-SMase. In addition, proteolytic degradation of A-SMase also did not affect SAPK/JNK activation by ultraviolet (UV-C) irradiation, arguing against a general role of A-SMase in stress-mediated responses. Furthermore, fibroblasts from Niemann–Pick A patients deficient in A-SMase did not show altered activation of SAPK/JNK in response to either TNF or UV-C. These results suggest that TR55 can activate SAPK/JNK without direct participation of sphingomyelinases or ceramide.
7
Fritz, Gerhard, i Bernd Kaina. "Late Activation of Stress Kinases (SAPK/JNK) by Genotoxins Requires the DNA Repair Proteins DNA-PKcs and CSB". Molecular Biology of the Cell 17, nr 2 (luty 2006): 851–61. http://dx.doi.org/10.1091/mbc.e05-07-0606.
Pełny tekst źródłaStreszczenie:
Although genotoxic agents are powerful inducers of stress kinases (SAPK/JNK), the contribution of DNA damage itself to this response is unknown. Therefore, SAPK/JNK activation of cells harboring specific defects in DNA damage-recognition mechanisms was studied. Dual phosphorylation of SAPK/JNK by the genotoxin methyl methanesulfonate (MMS) occurred in two waves. The early response (≤2 h after exposure) was similar in cells knockout for ATM, PARP, p53, and CSB or defective in DNA-PKcs compared with wild-type cells. The late response however (≥4 h), was drastically reduced in DNA-PKcs and Cockayne's syndrome B (CSB)-deficient cells. Similar results were obtained with human cells lacking DNA-PKcs and CSB. Activation of SAPK/JNK by MMS was not affected upon inhibition of base excision repair (BER), indicating base damage itself does not signal to SAPK/JNK. Because SAPK/JNK activation was attenuated in nongrowing cells, DNA replication-dependent processing of lesions, involving DNA-PKcs and CSB, appears to be required. DNA-PKcs coprecipitates with SEK1/MKK4 and SAPK/JNK, supporting a role of DNA-PKcs in SAPK/JNK activation. In this process, Rho GTPases are involved since inhibition of Rho impairs MMS-induced signaling to SAPK/JNK. The data show that sensing of DNA damage by DNA-PKcs and CSB causes a delayed SEK1/MKK4-mediated dual phosphorylation of SAPK/JNK.
8
Wu, Qihan. "Dual Specificity Phosphotase 18, Interacting with SAPK, Dephosphorylates SAPK and Inhibits SAPK/JNK Signal Pathway in vivo". Frontiers in Bioscience 11, nr 1 (2006): 2714. http://dx.doi.org/10.2741/2001.
Pełny tekst źródła
9
Chen, Guofeng, Baoqiang Liu, Jiajun Chen, Hongyu Liu, Beiping Tan, Xiaohui Dong, Qihui Yang, Shuyan Chi, Shuang Zhang i Min Yao. "Supplementing Sulfate-Based Alginate Polysaccharide Improves Pacific White Shrimp (Litopenaeus vannamei) Fed Fishmeal Replacement with Cottonseed Protein Concentrate: Effects on Growth, Intestinal Health, and Disease Resistance". Aquaculture Nutrition 2022 (8.02.2022): 1–21. http://dx.doi.org/10.1155/2022/7132362.
Pełny tekst źródłaStreszczenie:
Sulfate-based alginate polysaccharide (SAP) is a novelty marine prebiotic. To investigate the beneficial effects of SAP in Pacific white shrimp (Litopenaeus vannamei) fed low-fishmeal diets, six diets (whole fishmeal group: FM; fishmeal replacement with cottonseed protein concentrate and SAP supplementary groups: SAP0, SAP1, SAP2, SAP3, and SAP4) were formulated and fed shrimp for 56 days. The results showed that SAP2 and SAP3 groups reached the best weight gain and specific growth rate ( P < 0.05 ). In serum, the activities of lysozyme and acid phosphatase showed the trend of firstly increased and then decreased ( P < 0.05 ). In the gut, the highest activities of trypsin, lipase, and amylase were found in SAP2 and SAP3 groups ( P < 0.05 ); the histological indexes gradually improved with SAP levels increased ( P < 0.05 ); sequencing of microbiota revealed that the composition and structure of microbiota have been improved, especially in the decreasing abundance of Vibrio, Pseudoalteromonas, and Candidatus Bacilloplasma at genus level. Besides, transcriptomics revealed a degree of similarity in differential gene expression patterns in shrimp; the comparison of RNA-Seq and qRT-PCR verified that SAP improved antioxidant and immunity in shrimp. The challenge revealed that SAP strengthened the resistance against Vibrio parahaemolyticus. Totally, the supplementary SAP to low-fishmeal diets improved growth, intestinal health, and disease resistance in shrimp. Based on the polynomial curve analysis of specific growth rate among SAPs groups, the optimum SAP supplementary level was 1.91%.
10
Yoshida, Kiyotsugu, Ralph Weichselbaum, Surender Kharbanda i Donald Kufe. "Role for Lyn Tyrosine Kinase as a Regulator of Stress-Activated Protein Kinase Activity in Response to DNA Damage". Molecular and Cellular Biology 20, nr 15 (1.08.2000): 5370–80. http://dx.doi.org/10.1128/mcb.20.15.5370-5380.2000.
Pełny tekst źródłaStreszczenie:
ABSTRACT The cellular response to DNA damage includes activation of the nuclear Lyn protein tyrosine kinase. Using cells deficient in Lyn expression, the present studies demonstrate that Lyn is required in part for induction of the stress-activated protein kinase (SAPK) in the response to 1-β-d-arabinofuranosylcytosine (ara-C) and other genotoxic agents. By contrast, exposure of Lyn-deficient cells to ara-C, ionizing radiation, or cisplatin had no effect on activation of extracellular signal-regulated protein kinase or p38 mitogen-activated protein kinase. Similar findings were obtained in cells stably expressing a kinase-inactive, dominant-negative Lyn(K-R) mutant. Coexpression studies demonstrate that Lyn, but not Lyn(K-R), induces SAPK activity. In addition, the results demonstrate that Lyn activates SAPK by an MKK7-dependent, SEK1-independent mechanism. As MEKK1 functions upstream to MKK7 and SAPK, the finding that a dominant-negative MEKK1(K-M) mutant blocks Lyn-induced SAPK activity supports involvement of the MEKK1→MKK7 pathway. The results also demonstrate that inhibition of Lyn-induced SAPK activity abrogates the apoptotic response of cells to genotoxic stress. These findings indicate that activation of SAPK by DNA damage is mediated in part by Lyn and that the Lyn→MEKK1→MKK7→SAPK pathway is functional in the induction of apoptosis by genotoxic agents.
11
Tokuda, H., K. Hirade, X. Wang, Y. Oiso i O. Kozawa. "Involvement of SAPK/JNK in basic fibroblast growth factor-induced vascular endothelial growth factor release in osteoblasts". Journal of Endocrinology 177, nr 1 (1.04.2003): 101–7. http://dx.doi.org/10.1677/joe.0.1770101.
Pełny tekst źródłaStreszczenie:
We previously reported that basic fibroblast growth factor (FGF-2) activates p44/p42 mitogen-activated protein (MAP) kinase resulting in the stimulation of vascular endothelial growth factor (VEGF) release in osteoblast-like MC3T3-E1 cells and that FGF-2-activated p38 MAP kinase negatively regulates VEGF release. In the present study, we investigated the involvement of stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) in FGF-2-induced VEGF release in these cells. FGF-2 markedly induced the phosphorylation of SAPK/JNK. SP600125, an inhibitor of SAPK/JNK, markedly reduced the FGF-2-induced VEGF release. SP600125 suppressed the FGF-2-induced phosphorylation of SAPK/JNK without affecting the phosphorylation of p44/p42 MAP kinase or p38 MAP kinase induced by FGF-2. PD98059, an inhibitor of upstream kinase of p44/p42 MAP kinase, or SB203580, an inhibitor of p38 MAP kinase, failed to affect the FGF-2-induced phosphorylation of SAPK/JNK. A combination of SP600125 and SB203580 suppressed the FGF-2-stimulated VEGF release in an additive manner. These results strongly suggest that FGF-2 activates SAPK/JNK in osteoblasts, and that SAPK/JNK plays a part in FGF-2-induced VEGF release.
12
Shi, Chong-Shan, Joseph M. Tuscano, Owen N. Witte i John H. Kehrl. "GCKR Links the Bcr-Abl Oncogene and Ras to the Stress-Activated Protein Kinase Pathway". Blood 93, nr 4 (15.02.1999): 1338–45. http://dx.doi.org/10.1182/blood.v93.4.1338.
Pełny tekst źródłaStreszczenie:
Abstract The Bcr-Abl oncogene, found in Philadelphia chromosome-positive myelogenous leukemia (CML), activates Ras and triggers the stress-activated protein kinase (SAPK or Jun NH2-terminal kinase [JNK]) pathway. Interruption of Ras or SAPK activation dramatically reduces Bcr-Abl–mediated transformation. Here, we report that Bcr-Abl through a Ras-dependent pathway signals the serine/threonine protein kinase GCKR (Germinal Center Kinase Related) leading to SAPK activation. Either an oncogenic form of Ras or Bcr-Abl enhances GCKR catalytic activity and its activation of SAPK, whereas inhibition of GCKR impairs Bcr-Abl–induced SAPK activation. Bcr-Abl mutants that are impaired for GCKR activation are also unable to activate SAPK. Consistent with GCKR being a functional target in CML, GCKR is constitutively active in CML cell lines and found in association with Bcr-Abl. Our results indicate that GCKR is a downstream target of Bcr-Abl and strongly implicate GCKR as a mediator of Bcr-Abl in its transformation of cells.
13
Shi, Chong-Shan, Joseph M. Tuscano, Owen N. Witte i John H. Kehrl. "GCKR Links the Bcr-Abl Oncogene and Ras to the Stress-Activated Protein Kinase Pathway". Blood 93, nr 4 (15.02.1999): 1338–45. http://dx.doi.org/10.1182/blood.v93.4.1338.404k27_1338_1345.
Pełny tekst źródłaStreszczenie:
The Bcr-Abl oncogene, found in Philadelphia chromosome-positive myelogenous leukemia (CML), activates Ras and triggers the stress-activated protein kinase (SAPK or Jun NH2-terminal kinase [JNK]) pathway. Interruption of Ras or SAPK activation dramatically reduces Bcr-Abl–mediated transformation. Here, we report that Bcr-Abl through a Ras-dependent pathway signals the serine/threonine protein kinase GCKR (Germinal Center Kinase Related) leading to SAPK activation. Either an oncogenic form of Ras or Bcr-Abl enhances GCKR catalytic activity and its activation of SAPK, whereas inhibition of GCKR impairs Bcr-Abl–induced SAPK activation. Bcr-Abl mutants that are impaired for GCKR activation are also unable to activate SAPK. Consistent with GCKR being a functional target in CML, GCKR is constitutively active in CML cell lines and found in association with Bcr-Abl. Our results indicate that GCKR is a downstream target of Bcr-Abl and strongly implicate GCKR as a mediator of Bcr-Abl in its transformation of cells.
14
Kaneki, Masao, Surender Kharbanda, Pramod Pandey, Kiyotsugu Yoshida, Mutsuhiro Takekawa, Jiing-Ren Liou, Richard Stone i Donald Kufe. "Functional Role for Protein Kinase Cβ as a Regulator of Stress-Activated Protein Kinase Activation and Monocytic Differentiation of Myeloid Leukemia Cells". Molecular and Cellular Biology 19, nr 1 (1.01.1999): 461–70. http://dx.doi.org/10.1128/mcb.19.1.461.
Pełny tekst źródłaStreszczenie:
ABSTRACT Human myeloid leukemia cells respond to 12-O-tetradecanoylphorbol-13-acetate (TPA) and other activators of protein kinase C (PKC) with induction of monocytic differentiation. The present studies demonstrated that treatment of U-937 and HL-60 myeloid leukemia cells with TPA, phorbol-12,13-dibutyrate, or bryostatin 1 was associated with the induction of stress-activated protein kinase (SAPK). In contrast, TPA-resistant TUR and HL-525 cell variants deficient in PKCβ failed to respond to activators of PKC with the induction of SAPK. A direct role for PKCβ in TPA-induced SAPK activity in TUR and HL-525 cells that stably express PKCβ was confirmed. We showed that TPA induced the association of PKCβ with MEK kinase 1 (MEKK-1), an upstream effector of the SAPK/ERK kinase 1 (SEK1)→SAPK cascade. The results also demonstrated that PKCβ phosphorylated and activated MEKK-1 in vitro. The functional role of MEKK-1 in TPA-induced SAPK activity was further supported by the demonstration that the expression of a dominant negative MEKK-1 mutant abrogated this response. These findings indicate that PKCβ activation is necessary for activation of the MEKK-1→SEK1→SAPK cascade in the TPA response of myeloid leukemia cells.
15
Taruno, Akiyuki, Naomi Niisato i Yoshinori Marunaka. "Hypotonicity stimulates renal epithelial sodium transport by activating JNK via receptor tyrosine kinases". American Journal of Physiology-Renal Physiology 293, nr 1 (lipiec 2007): F128—F138. http://dx.doi.org/10.1152/ajprenal.00011.2007.
Pełny tekst źródłaStreszczenie:
We previously reported that hypotonic stress stimulated transepithelial Na+ transport via a pathway dependent on protein tyrosine kinase (PTK; Niisato N, Van Driessche W, Liu M, Marunaka Y. J Membr Biol 175: 63–77, 2000). However, it is still unknown what type of PTK mediates this stimulation. In the present study, we investigated the role of receptor tyrosine kinase (RTK) in the hypotonic stimulation of Na+ transport. In renal epithelial A6 cells, we observed inhibitory effects of AG1478 [an inhibitor of the EGF receptor (EGFR)] and AG1296 [an inhibitor of the PDGF receptor (PDGFR)] on both the hypotonic stress-induced stimulation of Na+ transport and the hypotonic stress-induced ligand-independent activation of EGFR. We further studied whether hypotonic stress activates members of the MAP kinase family, ERK1/2, p38 MAPK, and JNK/SAPK, via an RTK-dependent pathway. The present study indicates that hypotonic stress induced phosphorylation of ERK1/2 and JNK/SAPK, but not p38 MAPK, that the hypotonic stress-induced phosphorylation of ERK1/2 and JNK/SAPK was diminished by coapplication of AG1478 and AG1296, and that only JNK/SAPK was involved in the hypotonic stimulation of Na+ transport. A further study using cyclohexamide (a protein synthesis inhibitor) suggests that both RTK and JNK/SAPK contributed to the protein synthesis-independent early phase in hypotonic stress-induced Na+ transport, but not to the protein synthesis-dependent late phase. The present study also suggests involvement of phosphatidylinositol 3-kinase (PI3-kinase) in RTK-JNK/SAPK cascade-mediated Na+ transport. These observations indicate that 1) hypotonic stress activates JNK/SAPK via RTKs in a ligand-independent pathway, 2) the RTK-JNK/SAPK cascade acts as a mediator of hypotonic stress for stimulation of Na+ transport, and 3) PI3-kinase is involved in the RTK-JNK/SAPK cascade for the hypotonic stress-induced stimulation of Na+ transport.
16
Rausch, O., i C. J. Marshall. "Tyrosine 763 of the murine granulocyte colony-stimulating factor receptor mediates Ras-dependent activation of the JNK/SAPK mitogen-activated protein kinase pathway." Molecular and Cellular Biology 17, nr 3 (marzec 1997): 1170–79. http://dx.doi.org/10.1128/mcb.17.3.1170.
Pełny tekst źródłaStreszczenie:
The receptor for granulocyte colony-stimulating factor (G-CSF) can mediate differentiation and proliferation of hemopoietic cells. A proliferative signal is associated with activation of the ERK mitogen-activated protein kinase (MAPK) pathway. To determine whether other MAPK pathways are activated by G-CSF signalling, we have investigated activation of JNK/SAPK in cells proliferating in response to G-CSF. Here we show that G-CSF and interleukin-3 activate JNK/SAPK in two hemopoietic cell lines. The region of the G-CSF receptor required for G-CSF-induced JNK/SAPK activation is located within the C-terminal 68 amino acids of the cytoplasmic domain, which contains Tyr 763. Mutation of Tyr 763 to Phe completely blocks JNK/SAPK activation. However, the C-terminal 68 amino acids are not required for ERK2 activation. We show that activation of JNK/SAPK, like that of ERK2, is dependent on Ras but that higher levels of Ras-GTP are associated with activation of JNK/SAPK than with activation of ERK2. Two separate functional regions of the G-CSF receptor contribute to activation of Ras. The Y763F mutation reduces G-CSF-induced Ras activation from 30 to 35% Ras-GTP to 10 to 13% Ras-GTP. Low levels of Ras activation (10 to 13% Ras-GTP), which are sufficient for ERK2 activation, require only the 100 membrane-proximal amino acids. High levels of Ras-GTP provided by expression of oncogenic Ras are not sufficient to activate JNK/SAPK. An additional signal, also mediated by Tyr 763, is required for activation of JNK/SAPK.
17
Khan, Manzoor M., i Radhika Dandekar. "REGULATION OF SAPK/JNK PHOSPHORYLATION BY HISTAMINE IN SPLENOCYES (139.11)". Journal of Immunology 182, nr 1_Supplement (1.04.2009): 139.11. http://dx.doi.org/10.4049/jimmunol.182.supp.139.11.
Pełny tekst źródłaStreszczenie:
Abstract Histamine is an inflammatory mediator in allergic disease and asthma. A number of histamine-mediated effects result from cytokine interactions and through their signal transduction mechanisms. SAPK/JNK are stress activated kinases which are stimulated by a variety of factors including cytokines and play a role in inflammation, cell proliferation and differentiation. This study was designed to study the effects of histamine on the phosphorylation of SAPK/JNK in splenocytes. Splenocytes were isolated from C57/BL 6 mice and after treatment with various agonists and antagonists phosphorylated SAPK/JNK levels were analyzed by Western Blot Analysis. While histamine at 10-4 inhibited the phosphorylation of SAPK/JNK , all histamine receptor subset agonists, H1, H2, H3, and H4 upregulated SAPK/JNK phosphorylation suggesting a complex interaction of histamine receptors in this process. Splenocytes from TNF-á knockout mice were employed to determine the role of TNF-á in histamine-mediated effects. Histamine further suppressed not only the effects of histamine but also that of histamine H1, H2, and H3 agonists but not that of H4 agonist. The effects of H4 agonists were further pronounced in TNF-á knockout splenocytes. Our studies demonstrate a role of TNF-á in histamine H1, H2 and H3 receptor- mediated regulation of SAPK/JNK phosphorylation. Other proinflammatory cytokines may be involved in mediating the effects of histamine on SAPK/JNK, via H4 receptors. In conclusion, the effects of histamine on SAPK/JNK phosphorylation involve complex interaction of its receptor subsets and cytokines which may have relevance in allergic disease.
18
Ripeau, Jean-Sébastien, Francine Aumont, Pierre Belhumeur, Luis Ostrosky-Zeichner, John H. Rex i Louis de Repentigny. "Effect of the Echinocandin Caspofungin on Expression of Candida albicans Secretory Aspartyl Proteinases and Phospholipase In Vitro". Antimicrobial Agents and Chemotherapy 46, nr 9 (wrzesień 2002): 3096–100. http://dx.doi.org/10.1128/aac.46.9.3096-3100.2002.
Pełny tekst źródłaStreszczenie:
ABSTRACT Although the echinocandin caspofungin primarily inhibits the synthesis of cell wall 1,3-β-d-glucan, its fungicidal activity could also potentially perturb the expression of virulence factors involved in the ability of Candida albicans to cause infection. Expression of the C. albicans secretory aspartyl proteinase (SAP) and phospholipase B (PLB) virulence genes was determined by reverse transcription-PCR after the addition of caspofungin to cells grown for 15 h in Sabouraud dextrose broth. In cells that remained viable, expression of SAP1 to SAP3, SAP7 to SAP9, and PLB1 was unaltered after exposure to fungicidal concentrations (4 to 16 μg/ml) of caspofungin over a period of 7 h. However, expression of SAP5 increased steadily beginning 1 h after exposure to caspofungin. These results indicate that caspofungin is rapidly fungicidal against C. albicans, before any suppression of SAP or PLB1 gene expression can occur.
19
Sandra, Ferry, Junita Briskila i Ketherin Ketherin. "RANKL and TNF-α-induced JNK/SAPK Osteoclastogenic Signaling Pathway was Inhibited by Caffeic Acid in RAW-D Cells". Indonesian Journal of Cancer Chemoprevention 9, nr 2 (3.07.2018): 63. http://dx.doi.org/10.14499/indonesianjcanchemoprev9iss2pp63-67.
Pełny tekst źródłaStreszczenie:
Caffeic acid, a natural substance found majorly in fruits, grains, and herbs, is known to have therapeutic benefits. One of which is to inhibit bone resorption by targeting osteoclastogenesis through inhibition of the Cathepsin K, p38 Mitogen-activated Protein Kinase (MAPK), Nuclear Factor of Activated T-cells c1 (NFATc1) and Nuclear Factor kB (NFkB). Besides p38 MAPK, the c-Jun N-terminal kinase (JNK) / stress-activated protein kinases (SAPK), another member of MAPK family, has been reported to play important roles in osteoclastogenesis. Hence, current study was undertaken in order to investigate mechanism of Caffeic Acid towards JNK/SAPK pathway. Tartrate Resistant Acid Phosphatase (TRAP) staining was performed on caffeic acid-treated and RANKL-TNFα-induced RAW-D cells. Western blot analysis was performed to detect JNK/SAPK and phosphorylated-JNK/SAPK. Protein bands were quantified and statistically analyzed. Treatment of 10 μg/mL Caffeic Acid inhibited 20 ng/mL RANKL and 1 ng/mL TNFα-induced RAW-D differentiation into TRAP+ osteoclast-like polynuclear cells. Induction of 20 ng/mL of RANKL and 1 ng/mL of TNFα for 0.2 or 1 hour, significantly increase phosphorylation of JNK/SAPK as compared with control. Treatment of 10 µg/mL Caffeic Acid significantly inhibited the 20 ng/mL of RANKL and 1 ng/mL of TNFα-induced phosphorylation of JNK/SAPK. Taken together, Caffeic Acid could inhibit the RANKL and TNFα-induced osteoclastogenesis through JNK/SAPK.
20
Mosser, D. D., A. W. Caron, L. Bourget, C. Denis-Larose i B. Massie. "Role of the human heat shock protein hsp70 in protection against stress-induced apoptosis." Molecular and Cellular Biology 17, nr 9 (wrzesień 1997): 5317–27. http://dx.doi.org/10.1128/mcb.17.9.5317.
Pełny tekst źródłaStreszczenie:
Resistance to stress-induced apoptosis was examined in cells in which the expression of hsp70 was either constitutively elevated or inducible by a tetracycline-regulated transactivator. Heat-induced apoptosis was blocked in hsp70-expressing cells, and this was associated with reduced cleavage of the common death substrate protein poly(ADP-ribose) polymerase (PARP). Heat-induced cell death was correlated with the activation of the stress-activated protein kinase SAPK/JNK (c-Jun N-terminal kinase). Activation of SAPK/JNK was strongly inhibited in cells in which hsp70 was induced to a high level, indicating that hsp70 is able to block apoptosis by inhibiting signaling events upstream of SAPK/JNK activation. In contrast, SAPK/JNK activation was not inhibited by heat shock in cells with constitutively elevated levels of hsp70. Cells that constitutively overexpress hsp70 resist apoptosis induced by ceramide, a lipid signaling molecule that is generated by apoptosis-inducing treatments and is linked to SAPK/JNK activation. Similar to heat stress, resistance to ceramide-induced apoptosis occurs in spite of strong SAPK/JNK activation. Therefore, hsp70 is also able to inhibit apoptosis at some point downstream of SAPK/JNK activation. Since PARP cleavage is prevented in both cell lines, these results suggest that hsp70 is able to prevent the effector steps of apoptotic cell death. Processing of the CED-3-related protease caspase-3 (CPP32/Yama/apopain) is inhibited in hsp70-expressing cells; however, the activity of the mature enzyme is not affected by hsp70 in vitro. Caspase processing may represent a critical heat-sensitive target leading to cell death that is inhibited by the chaperoning function of hsp70. The inhibition of SAPK/JNK signaling and apoptotic protease effector steps by hsp70 likely contributes to the resistance to stress-induced apoptosis seen in transiently induced thermotolerance.
21
Kim, Jin Woo, Tong-Shin Chang, Ji Eun Lee, Sung-Ho Huh, Seung Woo Yeon, Wan Seok Yang, Cheol O. Joe i in. "Negative Regulation of the Sapk/Jnk Signaling Pathway by Presenilin 1". Journal of Cell Biology 153, nr 3 (24.04.2001): 457–64. http://dx.doi.org/10.1083/jcb.153.3.457.
Pełny tekst źródłaStreszczenie:
Presenilin 1 (PS1) plays a pivotal role in Notch signaling and the intracellular metabolism of the amyloid β-protein. To understand intracellular signaling events downstream of PS1, we investigated in this study the action of PS1 on mitogen-activated protein kinase pathways. Overexpressed PS1 suppressed the stress-induced stimulation of stress-activated protein kinase (SAPK)/c-Jun NH2-terminal kinase (JNK) in human embryonic kidney 293 cells. Interestingly, two functionally inactive PS1 mutants, PS1(D257A) and PS1(D385A), failed to inhibit UV-stimulated SAPK/JNK. Furthermore, H2O2- or UV-stimulated SAPK activity was higher in mouse embryonic fibroblast (MEF) cells from PS1-null mice than in MEF cells from PS+/+ mice. MEFPS1(−/−) cells were more sensitive to the H2O2-induced apoptosis than MEFPS1(+/+) cells. Ectopic expression of PS1 in MEFPS1(−/−) cells suppressed H2O2-stimulated SAPK/JNK activity and apoptotic cell death. Together, our data suggest that PS1 inhibits the stress-activated signaling by suppressing the SAPK/JNK pathway.
22
Matsushita, Moe, Takanori Nakamura, Hisashi Moriizumi, Hiroaki Miki i Mutsuhiro Takekawa. "Stress-responsive MTK1 SAPKKK serves as a redox sensor that mediates delayed and sustained activation of SAPKs by oxidative stress". Science Advances 6, nr 26 (czerwiec 2020): eaay9778. http://dx.doi.org/10.1126/sciadv.aay9778.
Pełny tekst źródłaStreszczenie:
Cells respond to oxidative stress by inducing intracellular signaling, including stress-activated p38 and JNK MAPK (SAPK) pathways, but the underlying mechanisms remain unclear. Here, we report that the MAP three kinase 1 (MTK1) SAPK kinase kinase (SAPKKK) functions as an oxidative-stress sensor that perceives the cellular redox state and transduces it into SAPK signaling. Following oxidative stress, MTK1 is rapidly oxidized and gradually reduced at evolutionarily conserved cysteine residues. These coupled oxidation-reduction modifications of MTK1 elicit its catalytic activity. Gene knockout experiments showed that oxidative stress–induced SAPK signaling is mediated by coordinated activation of the two SAPKKKs, MTK1 and apoptosis signal–regulating kinase 1 (ASK1), which have different time and dose-response characteristics. The MTK1-mediated redox sensing system is crucial for delayed and sustained SAPK activity and dictates cell fate decisions including cell death and interleukin-6 production. Our results delineate a molecular mechanism by which cells generate optimal biological responses under fluctuating redox environments.
23
Tatebe, Hisashi, i Kazuhiro Shiozaki. "Identification of Cdc37 as a Novel Regulator of the Stress-Responsive Mitogen-Activated Protein Kinase". Molecular and Cellular Biology 23, nr 15 (1.08.2003): 5132–42. http://dx.doi.org/10.1128/mcb.23.15.5132-5142.2003.
Pełny tekst źródłaStreszczenie:
ABSTRACT Eukaryotic cells utilize multiple mitogen-activated protein kinases (MAPKs) to transmit various extracellular stimuli to the nucleus. A subfamily of MAPKs that mediates environmental stress stimuli is also called stress-activated protein kinase (SAPK), which has crucial roles in cellular survival under stress conditions as well as inflammatory responses. Here we report that Cdc37, an evolutionarily conserved kinase-specific chaperone, is a positive regulator of Spc1 SAPK in the fission yeast Schizosaccharomyces pombe. Through a genetic screen, we have identified cdc37 as a mutation that compromises signaling through Spc1 SAPK. The Cdc37 protein physically interacts with Spc1, and the cdc37 mutation affects both the cellular level of the Spc1 protein and stress-induced Spc1 phosphorylation by Wis1 MAPK kinase (MAPKK). Consistently, expression of the stress response genes regulated by the Spc1 pathway is compromised in cdc37 mutant cells. On the other hand, a mutation in Hsp90, which often cooperates with Cdc37 in chaperoning protein kinases, does not affect Spc1 SAPK. These results suggest that Spc1 SAPK is a novel client protein for the Cdc37 chaperone, and the Cdc37 function is important to maintain the stability of the Spc1 protein and to facilitate stress signaling from Wis1 MAPKK to Spc1 SAPK.
24
Shi, Chong-Shan, Antonio Leonardi, John Kyriakis, Ulrich Siebenlist i John H. Kehrl. "TNF-Mediated Activation of the Stress-Activated Protein Kinase Pathway: TNF Receptor-Associated Factor 2 Recruits and Activates Germinal Center Kinase Related". Journal of Immunology 163, nr 6 (15.09.1999): 3279–85. http://dx.doi.org/10.4049/jimmunol.163.6.3279.
Pełny tekst źródłaStreszczenie:
Abstract TNF-induced activation of stress activated protein kinases (SAPKs, Jun NH2-terminal kinases) requires TNF receptor associated factor 2 (TRAF2). TRAF2 is a potent activator of a 95-kDa serine/threonine kinase termed germinal center kinase related (GCKR, also referred to as KHS1), which signals activation of the SAPK pathway. Consistent with a role for GCKR in TNF- induced SAPK activation, a kinase-inactive mutant of GCKR is a dominant negative inhibitor of TRAF2-induced SAPK activation. Here we show that TRAF2 interacts with GCKR. This interaction depended upon the TRAF domain of TRAF2 and the C-terminal 150 aa of GCKR. The full activation of GCKR by TRAF2 required the TRAF2 RING finger domain. TNF treatment of a T cell line, Jurkat, increased both GCRK and SAPK activity and enhanced the coimmunoprecipitation of GCKR with TRAF2. Similar results were found with the B cell line HS-Sultan. These findings are consistent with a model whereby TNF signaling results in the recruitment and activation of GCKR by TRAF2, which leads to SAPK activation.
25
Nagata, Yuka, i Kazuo Todokoro. "Requirement of Activation of JNK and p38 for Environmental Stress-Induced Erythroid Differentiation and Apoptosis and of Inhibition of ERK for Apoptosis". Blood 94, nr 3 (1.08.1999): 853–63. http://dx.doi.org/10.1182/blood.v94.3.853.415a12_853_863.
Pełny tekst źródłaStreszczenie:
C-Jun amino terminal kinase/stress-activated protein kinases (JNK/SAPK) and p38 subgroups of mitogen-activated protein kinases have been suggested to play a critical role in apoptosis, cell growth, and/or differentiation. We found that a short exposure of SKT6 cells, which respond to erythropoietin (Epo) and induce erythroid differentiation, to osmotic or heat shock induced transient activation of JNK/SAPK and p38 and inactivation of ERK and resulted in erythroid differentiation without Epo, whereas long exposure of the cells to these stresses induced prolonged activation/inactivation of the same kinases and caused apoptosis. Inhibition of JNK/SAPK and p38 resulted in inhibition of stress-induced erythroid differentiation and apoptosis. Inhibition of ERK had no effect on stress-induced erythroid differentiation, but stimulated apoptosis. Activation of p38 and/or JNK/SAPK for a short time caused erythroid differentiation without Epo, although its prolonged activation induced apoptosis. Activation of ERK suppressed stress-induced apoptosis. These results indicate that short cellular stresses, inducing transient activation of JNK/SAPK and p38, lead to cell differentiation rather than apoptosis. Furthermore, activation of JNK/SAPK and p38 is required for both cell differentiation and apoptosis, and the duration of their activation may determine the cell fate, cell differentiation, and apoptosis. In contrast, inactivation of ERK is required for stress-induced apoptosis but not cell differentiation.
26
Cannons, Jennifer L., Klaus P. Hoeflich, James R. Woodgett i Tania H. Watts. "Role of the Stress Kinase Pathway in Signaling Via the T Cell Costimulatory Receptor 4-1BB". Journal of Immunology 163, nr 6 (15.09.1999): 2990–98. http://dx.doi.org/10.4049/jimmunol.163.6.2990.
Pełny tekst źródłaStreszczenie:
Abstract 4-1BB is a member of the TNFR superfamily expressed on activated CD4+ and CD8+ T cells. 4-1BB can costimulate IL-2 production by resting primary T cells independently of CD28 ligation. In this study, we report signaling events following 4-1BB receptor aggregation using an Ak-restricted costimulation-dependent T cell hybridoma, C8.A3. Aggregation of 4-1BB on the surface of C8.A3 cells induces TNFR-associated factor 2 recruitment, which in turn recruits and activates apoptosis signal-regulating kinase-1, leading to downstream activation of c-Jun N-terminal/stress-activated protein kinases (JNK/SAPK). 4-1BB ligation also enhances anti-CD3-induced JNK/SAPK activation in primary T cells. Overexpression of a catalytically inactive form of apoptosis signal-regulating kinase-1 in C8.A3 T cells interferes with activation of the SAPK cascade and with IL-2 secretion, consistent with a critical role for JNK/SAPK activation in 4-1BB-dependent IL-2 production. Given the ability of both CD28 and 4-1BB to induce JNK/SAPK activation, we asked whether hyperosmotic shock, another inducer of this cascade, could function to provide a costimulatory signal to T cells. Osmotic shock of resting primary T cells in conjunction with anti-CD3 treatment was found to costimulate IL-2 production by the T cells, consistent with a pivotal role for JNK/SAPK in T cell costimulation.
27
Irving, Elaine A., i Mark Bamford. "Role of Mitogen- and Stress-Activated Kinases in Ischemic Injury". Journal of Cerebral Blood Flow & Metabolism 22, nr 6 (czerwiec 2002): 631–47. http://dx.doi.org/10.1097/00004647-200206000-00001.
Pełny tekst źródłaStreszczenie:
Protein kinase-mediated signaling cascades constitute the major route by which cells respond to their extracellular environment. Of these, three well-characterized mitogen-activated protein kinase (MAPK) signaling pathways are those that use the extracellular signal-regulated kinase (ERK1/2) or the stress-activated protein kinase (p38/SAPK2 or JNK/SAPK) pathways. Mitogenic stimulation of the MAPK-ERK1/2 pathway modulates the activity of many transcription factors, leading to biological responses such as proliferation and differentiation. In contrast, the p38/SAPK2 and JNK/SAPK (c-Jun amino-terminal kinase/stress-activated protein kinase) pathways are only weakly, if at all, activated by mitogens, but are strongly activated by stress stimuli. There is now a growing body of evidence showing that these kinase signaling pathways become activated following a variety of injury stimuli including focal cerebral ischemia. Whether their activation, however, is merely an epiphenomenon of the process of cell death, or is actually involved in the mechanisms underlying ischemia-induced degeneration, remains to be fully understood. This review provides an overview of the current understanding of kinase pathway activation following cerebral ischemia and discusses the evidence supporting a role for these kinases in the mechanisms underlying ischemia-induced cell death.
28
Muhammad Fandy Asyik, I Nyoman Sumaryadi i Deti Mulyati. "IMPLEMENTASI KEBIJAKAN SISTEM APLIKASI PELAYANAN KEPEGAWAIAN (SAPK) DI BADAN KEPEGAWAIAN DAN PENGEMBANGAN SUMBER DAYA MANUSIA KABUPATEN FAKFAK PROVINSI PAPUA BARAT". VISIONER : Jurnal Pemerintahan Daerah di Indonesia 13, nr 1 (30.04.2021): 1–12. http://dx.doi.org/10.54783/jv.v13i1.369.
Pełny tekst źródłaStreszczenie:
Sistem Aplikasi Pelayanan Kepegawaian (SAPK) merupakan pelayanan kepegawaian berbasis teknologi informasi yang terkoneksi secara online dan terintegrasi untuk digunakan oleh instansi pusat maupun pemerintah daerah sehingga akan meningkatkan pelayanan di bidang kepegawaian secara transparan dan objektif. BKPSDM Kabupaten Fakfak telah menerapkan sistem ini untuk mempercepat proses pelayanan kepegawaian sesuai dengan Perka BKN No. 20 Tahun 2008 meliputi pengadaan, kenaikan pangkat, pensiun dan peremajaan data.
Penelitian ini bersifat kualitatif Teknik pengumpulan data yang dilakukan melalui wawancara semi struktur dengan menggunakan pedoman wawancara, pengamatan (observasi) dan dokumentasi. Pemilihan informan dilakukan dengan cara Purposif sampling yaitu pemilihan informan dengan pertimbangan bahwa informan mengetahui hal yang akan diteliti dan Teknik analisis data yang digunakan 1). Reduksi Data (Data Data reduksi), 2). Penyajian Data (Data Displai) dan 3). Conclusion Drawing/Verivication (Pengambilan Keputusan/Verifikasi).
Hasil penelitian ini menunjukkan bahwa Implementasi Kebijakan SAPK di Pemerintah Kabupaten Fakfak telah berjalan tetapi belum optimal. Untuk pelayanan Pengadaan, Penetapan NIP dan Pelayanan pensiun sudah terimplementasi dengan baik, akan tetapi kenaikan pangkat belum memberikan dampak sebagaimana yang diharapkan. PNS yang naik pangkat menerima SK Kenpat-nya melebihi batas waktu periode Kenpat. Begitupun peremajaan data, masih terdapat PNS yang data SAPK, data DUK kepegawaiannya tidak sesuai dengan yang sebenarnya sehingga memperlambat proses pelayanannya.
Faktor penghambat dalam implementasi SAPK meliputi: belum tersedianya sumber daya dan personel yang memiliki keahlian sebagai analisis kepegawaian untuk memvalidasi data, dan jaringan internet yang mengalami gangguan. Sedangkan Faktor pendukung meliputi Faktor Komunikasi: adanya kebijakan secara tertulis dan adanya kejelasan dalam penyampaian pesan. Faktor sumber daya: tersedianya sumber daya staf, kemampuan staf sebagai sebagai operator Komputer, dan semua bersikap menerima kebijakan SAPK. Serta Upaya dalam mengoptimalkan implementasi kebijakan SAPK meliputi: Sosialisasi berupa Rapat. Mengikutsertakan staf Diklat analis kepegawaian dan semua personel yang mengoperasikan SAPK.
29
WANG, Xiantao, Jennifer L. MARTINDALE, Yusen LIU i Nikki J. HOLBROOK. "The cellular response to oxidative stress: influences of mitogen-activated protein kinase signalling pathways on cell survival". Biochemical Journal 333, nr 2 (15.07.1998): 291–300. http://dx.doi.org/10.1042/bj3330291.
Pełny tekst źródłaStreszczenie:
The mammalian response to stress is complex, often involving multiple signalling pathways that act in concert to influence cell fate. To examine potential interactions between the signalling cascades, we have focused on the effects of a model oxidant stress in a single cell type through an examination of the relative influences of mitogen-activated protein kinases (MAPKs) as well as two proposed apoptosis regulators, nuclear factor κB (NF-κB) and Bcl-2, in determining cell survival. Treatment of HeLa cells with H2O2 resulted in a time- and dose-dependent induction of apoptosis accompanied by sustained activation of all three MAPK subfamilies: extracellular signal-regulated protein kinase (ERK), c-Jun N-terminal kinase/stress-activated protein kinase (JNK/SAPK) and p38. This H2O2-induced apoptosis was markedly enhanced when ERK2 activation was selectively inhibited by PD098059. Apoptosis decreased when JNK/SAPK activation was inhibited by expression of a dominant negative mutant form of SAPK/ERK kinase 1. Inhibition of the p38 kinase activity with p38-specific inhibitors SB202190 and SB203580 had no effect on cell survival. Because NF-κB activation by H2O2 is potentially related to both the ERK and JNK/SAPK signalling pathways, we examined the effects of inhibiting the activation of NF-κB; this interference had no effect on the cellular response to H2O2. Overexpression of the anti-apoptotic protein Bcl-2 significantly decreased the apoptosis seen after treatment with H2O2 without altering ERK or JNK/SAPK activities. Our results suggest that ERK and JNK/SAPK act in opposition to influence cell survival in response to oxidative stress, whereas neither p38 nor NF-κB affects the outcome. Bcl-2 acts independently and downstream of ERK and JNK/SAPK to enhance the survival of H2O2-treated cells.
30
Smith, Deborah A., Susan Nicholls, Brian A. Morgan, Alistair J. P. Brown i Janet Quinn. "A Conserved Stress-activated Protein Kinase Regulates a Core Stress Response in the Human PathogenCandida albicans". Molecular Biology of the Cell 15, nr 9 (wrzesień 2004): 4179–90. http://dx.doi.org/10.1091/mbc.e04-03-0181.
Pełny tekst źródłaStreszczenie:
Previous work has implicated the Hog1 stress-activated protein kinase (SAPK) in osmotic and oxidative stress responses in the human pathogen Candida albicans. In this study, we have characterized the role of Hog1 in mediating these and other stress responses in C. albicans. We provide evidence that a SAPK-dependent core stress response exists in this pathogen. The Hog1 SAPK is phosphorylated and it accumulates in the nucleus in response to diverse stress conditions. In addition, we have identified Hog1-regulated genes that are induced in response to stress conditions that activate Hog1. These analyses reveal both activator and repressor functions for the Hog1 SAPK. Our results also demonstrate that stress cross-protection, a classical hallmark of the core stress response, occurs in C. albicans between stresses that activate the Hog1 SAPK. Importantly, we find that the core stress response in C. albicans has adapted to the environmental niche of this human pathogen. This niche specificity is reflected by the specific environmental conditions that drive the Hog1-regulated core stress response in C. albicans and by differences in the molecular circuitry that control this response.
31
McNEILL, Helen, Axel KNEBEL, J. Simon C. ARTHUR, Ana CUENDA i Philip COHEN. "A novel UBA and UBX domain protein that binds polyubiquitin and VCP and is a substrate for SAPKs". Biochemical Journal 384, nr 2 (23.11.2004): 391–400. http://dx.doi.org/10.1042/bj20041498.
Pełny tekst źródłaStreszczenie:
A widely expressed protein containing UBA (ubiquitin-associated) and UBX (ubiquitin-like) domains was identified as a substrate of SAPKs (stress-activated protein kinases). Termed SAKS1 (SAPK substrate-1), it was phosphorylated efficiently at Ser200in vitro by SAPK3/p38γ, SAPK4/p38δ and JNK (c-Jun N-terminal kinase), but weakly by SAPK2a/p38α, SAPK2b/p38β2 or ERK (extracellular-signal-regulated kinase) 2. Ser200, situated immediately N-terminal to the UBX domain, became phosphorylated in HEK-293 (human embryonic kidney) cells in response to stressors. Phosphorylation was not prevented by SB 203580 (an inhibitor of SAPK2a/p38α and SAPK2b/p38β2) and/or PD 184352 (which inhibits the activation of ERK1 and ERK2), and was similar in fibroblasts lacking both SAPK3/p38γ and SAPK4/p38δ or JNK1 and JNK2. SAKS1 bound ubiquitin tetramers and VCP (valosin-containing protein) in vitro via the UBA and UBX domains respectively. The amount of VCP in cell extracts that bound to immobilized GST (glutathione S-transferase)–SAKS1 was enhanced by elevating the level of polyubiquitinated proteins, while SAKS1 and VCP in extracts were coimmunoprecipitated with an antibody raised against S5a, a component of the 19 S proteasomal subunit that binds polyubiquitinated proteins. PNGase (peptide N-glycanase) formed a 1:1 complex with VCP and, for this reason, also bound to immobilized GST–SAKS1. We suggest that SAKS1 may be an adaptor that directs VCP to polyubiquitinated proteins, and PNGase to misfolded glycoproteins, facilitating their destruction by the proteasome.
32
Sufi, Wasiah, i Dwi Herlinda. "PENERAPAN SISTEM APLIKASI PELAYANAN KEPEGAWAIAN (SAPK) BERBASIS ONLINE PADA BADAN KEPEGAWAIAN DAERAH KOTA PEKANBARU". Jurnal Niara 9, nr 2 (4.01.2017): 102–8. http://dx.doi.org/10.31849/nia.v9i2.2103.
Pełny tekst źródłaStreszczenie:
This research was conducted at the office of the Badan Kepegawaian Daerah of Pekanbaru. Based on their initial observations of problems in implementing Employment Service Application System (SAPK Online) at the Badan Kepegawaian Daerah of Pekanbaru.in terms of human resources mampun Technology. This study focuses on the Implementation of E-Government through Employment Service Application System (SAPK Online): (1). To Knowing how the implementation of E-Government by using the Employment Service Application System (SAPK Online) at the Badan Kepegawaian Daerah of Pekanbaru.. (2). For Knowing the factors inhibiting the implementation of E-Government by using the Employment Service Application System (SAPK Online) at the Badan Kepegawaian Daerah of Pekanbaru.. This study is a qualitative study with the primary objective to describe and depict in detail and depth about how the implementation of E-Government in personnel administration through the Employment Service Application System (SAPK Online). Then the data analysis techniques used in this research was qualitative descriptive analysis, which is a technique that tries to describe things that are special to the data obtained through observation, interviews and documentation so that a qualitative data, to be analyzed further to become a conclusions according to the indicators that have been determined by the authors.
33
Nagata, Yuka, Friedemann Kiefer, Takeshi Watanabe i Kazuo Todokoro. "Activation of Hematopoietic Progenitor Kinase-1 by Erythropoietin". Blood 93, nr 10 (15.05.1999): 3347–54. http://dx.doi.org/10.1182/blood.v93.10.3347.410k06_3347_3354.
Pełny tekst źródłaStreszczenie:
Hematopoietic progenitor kinase-1 (HPK1), which is expressed predominantly in hematopoietic cells, was identified as a mammalian Ste20 homologue that, upon transfection, leads to activation of JNK/SAPK in nonhematopoietic cells. The JNK/SAPK pathway is activated by various environmental stresses and proinflammatory and hematopoietic cytokines. Upstream activators of HPK1 currently remain elusive, and its precise role in hematopoiesis has yet to be defined. We therefore examined the possible involvement of HPK1 in erythropoietin (Epo) and environmental stress-induced JNK/SAPK activation in the Epo-dependent FD-EPO cells and Epo-responsive SKT6 cells. We found that Epo, but not environmental stresses, induced rapid and transient activation of HPK1, whereas both induced activation of JNK/SAPK. A screen for HPK1 binding proteins identified the hematopoietic cell-specific protein 1 (HS1) as a potential HPK1 interaction partner. We found HPK1 constitutively associated with HS1 and that HS1 was tyrosine-phosphorylated in response to cellular stresses as well as Epo stimulation. Furthermore, antisense oligonucleotides to HPK1 suppressed Epo-dependent cell growth and Epo-induced erythroid differentiation. We therefore conclude that Epo induces activation of both HPK1 and HS1, whereas cellular stresses activate only HS1, and that the HPK1-JNK/SAPK pathway is involved in Epo-induced growth and differentiation signals.
34
ZHU, Ping, Weisheng XIONG, Gary RODGERS i E. Eva QWARNSTROM. "Regulation of interleukin 1 signalling through integrin binding and actin reorganization: disparate effects on NF-κB and stress kinase pathways". Biochemical Journal 330, nr 2 (1.03.1998): 975–81. http://dx.doi.org/10.1042/bj3300975.
Pełny tekst źródłaStreszczenie:
Interleukin 1 (IL-1)-mediated gene regulation is dependent on cell-matrix interactions. Both IL-1-activated pathways, nuclear factor κB (NF-κB) and the stress-activated protein kinase (SAPK), can be regulated by cell adhesion and changes in the cytoskeleton, suggesting that cell-matrix effects on IL-1 responses are initiated in part though effects on signal transduction. Here we show that IL-1-induced transient alterations in cell shape and in the cytoskeleton in fibronectin attached cells are correlated with effects on peak activity of NF-κB and SAPK. Cells on fibronectin showed a 1.5-2-fold enhancement in IL-1-induced NF-κB activity compared with levels in cells on poly(L-lysine) or bare tissue culture plates. The effect was increased with increasing concentrations of fibronectin and was most prominent at lower concentrations of IL-1. In contrast, fibronectin attachment caused an approx. 50% decrease in the IL-1 activation of SAPK, eliminating the peak activity after 15 min of stimulation with IL-1. IL-1-induced NF-κB activity showed a successive, substratum-independent increase during 4 h of attachment and spreading, whereas the inhibitory effect of fibronectin on the SAPK pathway was induced at the initial stages of attachment. Further, the addition of a peptide containing the motif RGD resulted in a 40% decrease in NF-κB activity in cells on fibronectin, largely accounted for by an effect on the p50/p65 heterodimer. Similarly, blocking of integrin aggregation by RGD-containing peptide resulted in a total abrogation of the fibronectin effect on IL-1-induced SAPK activity. The results demonstrate disparate effects of cell adhesion on the activation by IL-1 of the NF-κB and SAPK pathways. Thus fibronectin attachment causes an up-regulation of NF-κB activity in the presence of IL-1, whereas in contrast it results in a pronounced decrease in IL-1-induced SAPK activity.
35
Kharbanda, Surender, Pramod Pandey, Teruo Yamauchi, Shailender Kumar, Masao Kaneki, Vijay Kumar, Ajit Bharti i in. "Activation of MEK Kinase 1 by the c-Abl Protein Tyrosine Kinase in Response to DNA Damage". Molecular and Cellular Biology 20, nr 14 (15.07.2000): 4979–89. http://dx.doi.org/10.1128/mcb.20.14.4979-4989.2000.
Pełny tekst źródłaStreszczenie:
ABSTRACT The c-Abl protein tyrosine kinase is activated by certain DNA-damaging agents and regulates induction of the stress-activated c-Jun N-terminal protein kinase (SAPK). Here we show that nuclear c-Abl associates with MEK kinase 1 (MEKK-1), an upstream effector of the SEK1→SAPK pathway, in the response of cells to genotoxic stress. The results demonstrate that the nuclear c-Abl binds to MEKK-1 and that c-Abl phosphorylates MEKK-1 in vitro and in vivo. Transient-transfection studies with wild-type and kinase-inactive c-Abl demonstrate c-Abl kinase-dependent activation of MEKK-1. Moreover, c-Abl activates MEKK-1 in vitro and in response to DNA damage. The results also demonstrate that c-Abl induces MEKK-1-mediated phosphorylation and activation of SEK1-SAPK in coupled kinase assays. These findings indicate that c-Abl functions upstream of MEKK-1-dependent activation of SAPK in the response to genotoxic stress.
36
Thompson, Stuart A., Omer L. Shedd, Kevin C. Ray, Michael H. Beins, Jesse P. Jorgensen i Martin J. Blaser. "Campylobacter fetus Surface Layer Proteins Are Transported by a Type I Secretion System". Journal of Bacteriology 180, nr 24 (15.12.1998): 6450–58. http://dx.doi.org/10.1128/jb.180.24.6450-6458.1998.
Pełny tekst źródłaStreszczenie:
ABSTRACT The virulence of Campylobacter fetus, a bacterial pathogen of ungulates and humans, is mediated in part by the presence of a paracrystalline surface layer (S-layer) that confers serum resistance. The subunits of the S-layer are S-layer proteins (SLPs) that are secreted in the absence of an N-terminal signal sequence and attach to either type A or B C. fetus lipopolysaccharide in a serospecific manner. Antigenic variation of multiple SLPs (encoded bysapA homologs) of type A strain 23D occurs by inversion of a promoter-containing DNA element flanked by two sapAhomologs. Cloning and sequencing of the entire 6.2-kb invertible region from C. fetus 23D revealed a probable 5.6-kb operon of four overlapping genes (sapCDEF, with sizes of 1,035, 1,752, 1,284, and 1,302 bp, respectively) transcribed in the opposite direction from sapA. The four genes also were present in the invertible region of type B strain 84-107 and were virtually identical to their counterparts in the type A strain. Although SapC had no database homologies, SapD, SapE, and SapF had predicted amino acid homologies with type I protein secretion systems (typified byEscherichia coli HlyBD/TolC or Erwinia chrysanthemi PrtDEF) that utilize C-terminal secretion signals to mediate the secretion of hemolysins, leukotoxins, or proteases from other bacterial species. Analysis of the C termini of four C. fetus SLPs revealed conserved structures that are potential secretion signals. A C. fetus sapD mutant neither produced nor secreted SLPs. E. coli expressing C. fetus sapA and sapCDEF secreted SapA, indicating that thesapCDEF genes are sufficient for SLP secretion. C. fetus SLPs therefore are transported to the cell surface by a type I secretion system.
37
Iordanov, M. S., D. Pribnow, J. L. Magun, T. H. Dinh, J. A. Pearson, S. L. Chen i B. E. Magun. "Ribotoxic stress response: activation of the stress-activated protein kinase JNK1 by inhibitors of the peptidyl transferase reaction and by sequence-specific RNA damage to the alpha-sarcin/ricin loop in the 28S rRNA." Molecular and Cellular Biology 17, nr 6 (czerwiec 1997): 3373–81. http://dx.doi.org/10.1128/mcb.17.6.3373.
Pełny tekst źródłaStreszczenie:
Inhibition of protein synthesis per se does not potentiate the stress-activated protein kinases (SAPKs; also known as cJun NH2-terminal kinases [JNKs]). The protein synthesis inhibitor anisomycin, however, is a potent activator of SAPKs/JNKs. The mechanism of this activation is unknown. We provide evidence that in order to activate SAPK/JNK1, anisomycin requires ribosomes that are translationally active at the time of contact with the drug, suggesting a ribosomal origin of the anisomycin-induced signaling to SAPK/JNK1. In support of this notion, we have found that aminohexose pyrimidine nucleoside antibiotics, which bind to the same region in the 28S rRNA that is the target site for anisomycin, are also potent activators of SAPK/JNK1. Binding of an antibiotic to the 28S rRNA interferes with the functioning of the molecule by altering the structural interactions of critical regions. We hypothesized, therefore, that such alterations in the 28S rRNA may act as recognition signals to activate SAPK/JNK1. To test this hypothesis, we made use of two ribotoxic enzymes, ricin A chain and alpha-sarcin, both of which catalyze sequence-specific RNA damage in the 28S rRNA. Consistent with our hypothesis, ricin A chain and alpha-sarcin were strong agonists of SAPK/JNK1 and of its activator SEK1/MKK4 and induced the expression of the immediate-early genes c-fos and c-jun. As in the case of anisomycin, ribosomes that were active at the time of exposure to ricin A chain or alpha-sarcin were able to initiate signal transduction from the damaged 28S rRNA to SAPK/JNK1 while inactive ribosomes were not.
38
Sanghera, J. S., S. L. Weinstein, M. Aluwalia, J. Girn i S. L. Pelech. "Activation of multiple proline-directed kinases by bacterial lipopolysaccharide in murine macrophages." Journal of Immunology 156, nr 11 (1.06.1996): 4457–65. http://dx.doi.org/10.4049/jimmunol.156.11.4457.
Pełny tekst źródłaStreszczenie:
Abstract Bacterial LPS stimulation of murine macrophages leads to increased tyrosine phosphorylation and activation of the 42- and 44-kDa mitogen-activated protein kinases (MAPK) and the activation of stress-activated protein kinases (SAPK)/c-Jun N-terminal kinase (JNK) and p38, related to the high osmolarity glycerol protein kinase in Saccharomyces cerevisiae (HOG1). LPS caused a rapid increase (10 min) in phosphotransferase activity toward myelin basic protein (MBP), a polypeptide that encompassed the first 169 residues of c-Jun fused to gluthathione S-transferase (GST-c-Jun (1-169)) and 27-kDa heat shock protein (hsp27). MonoQ fractionation of cell extracts resolved phosphotransferase activity peaks toward MBP, GST-c-Jun (1-169), and hsp27, which contained MAPK, SAPK/JNK, and MAPKAPK2, respectively, as indicated by immunoblotting data. In RAW 264.7 macrophages, LPS stimulation of MAPKAPK2, a substrate of p38 HOG1 and MAPK, appeared to occur predominantly via p38 HOG1 and not the MAPK. PMA, which activated the MAPK as potently as LPS, did not strongly activate MAPKAPK2, as assessed by hsp27 phosphorylation. Consistent with p38 HOG1-mediating LPS activation of MAPKAPK2, treatment with LPS, but not PMA, increased the tyrosine phosphorylation of p38 HOG1, a modification known to elevate the enzymatic capacity of this kinase. In LPS-treated cells, the activity of SAPK/JNK was increased 5- to 10-fold, as measured by precipitating SAPK/JNK with Abs or immobilized GST-c-Jun and performing an in vitro kinase assay. In addition, the kinases thought to be upstream of SAPK/JNK, SAPK/ERK kinase 1 (SEK1), and MAPK/ERK kinase kinase 1 (MEKK1), were activated following LPS, but not PMA, exposure (5-fold and 2.5-fold, respectively.
39
Liu, Xixi, Zhiyong Li, Yuxuan Hou, Yifeng Wang, Huimei Wang, Xiaohong Tong, Hejun Ao i Jian Zhang. "Protein Interactomic Analysis of SAPKs and ABA-Inducible bZIPs Revealed Key Roles of SAPK10 in Rice Flowering". International Journal of Molecular Sciences 20, nr 6 (21.03.2019): 1427. http://dx.doi.org/10.3390/ijms20061427.
Pełny tekst źródłaStreszczenie:
As core components of ABA signaling pathway, SnRK2s (Sucrose nonfermenting1–Related protein Kinase 2) bind to and phosphorylate AREB/ABF (ABA responsive element binding protein/ABRE-binding factor) transcriptional factors, particularly bZIPs (basic region-leucine zipper), to participate in various biological processes, including flowering. Rice contains 10 SnRK2 members denoted as SAPK1-10 (Stress-Activated Protein Kinase) and dozens of bZIPs. However, which of the SAPKs and bZIPs pair and involve in ABA signaling remains largely unknown. In this study, we carried out a systematical protein-protein interactomic analysis of 10 SAPKs and 9 ABA-inducible bZIPs using yeast-two-hybrid technique, and identified 14 positive interactions. The reliability of Y2H work was verified by in vitro pull-down assay of the key flowering regulator bZIP77 with SAPK9 and SAPK10, respectively. Moreover, SAPK10 could phosphorylate bZIP77 in vitro. Over-expression of SAPK10 resulted in earlier flowering time, at least partially through regulating the FAC-MADS15 pathway. Conclusively, our results provided an overall view of the SAPK-bZIP interactions, and shed novel lights on the mechanisms of ABA-regulated rice flowering.
40
Kim, Do Kyun, Eun Sook Cho, Je Kyung Seong i Hong-Duck Um. "Adaptive concentrations of hydrogen peroxide suppress cell death by blocking the activation of SAPK/JNK pathway". Journal of Cell Science 114, nr 23 (1.12.2001): 4329–34. http://dx.doi.org/10.1242/jcs.114.23.4329.
Pełny tekst źródłaStreszczenie:
Low levels of H2O2 can induce cellular resistance to subsequent higher levels of H2O2. By using human U937 leukemia cells, it was previously shown that such an adaptive response can be induced without increasing the cellular capacity to degrade H2O2, thus conferring on the cells a cross-resistance to other stimuli such as serum withdrawal and C2-ceramide. In this study, it was found that stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) acts as a common mediator of the cell death induced by high H2O2 concentrations, serum withdrawal and C2-ceramide. Although SAPK/JNK activation by H2O2 was mediated by two upstream mitogen-activated protein kinase (MAPK) kinases MKK4 and MKK7, only MKK7 played such a role in serum withdrawal and C2-ceramide. Interestingly, all these lethal stimuli failed to activate SAPK/JNK and its upstream kinases in the cells that were pretreated with low adaptive concentrations of H2O2. By contrast, the phosphorylation levels of extracellular signal-regulated kinase and p38 MAPK were not significantly influenced by this H2O2 pretreatment. Inducing the SAPK/JNK-suppressing effect of H2O2 required a time lag, which correlated with the time lag required for the induction of the adaptive response. Overall, the results suggest that H2O2 adaptation confers on cells a resistance to multiple stimuli by specifically blocking their ability to activate the SAPK/JNK pathways.
41
Chauhan, Dharminder, Surender Kharbanda, Atsushi Ogata, Mitsuyoshi Urashima, Gerrard Teoh, Michael Robertson, Donald W. Kufe i Kenneth C. Anderson. "Interleukin-6 Inhibits Fas-Induced Apoptosis and Stress-Activated Protein Kinase Activation in Multiple Myeloma Cells". Blood 89, nr 1 (1.01.1997): 227–34. http://dx.doi.org/10.1182/blood.v89.1.227.
Pełny tekst źródłaStreszczenie:
Abstract Fas belongs to the family of type-1 membrane proteins that transduce apoptotic signals. In the present studies, we characterized signaling during Fas-induced apoptosis in RPMI-8226 and IM-9 multiple myeloma (MM) derived cell lines as well as patient plasma cell leukemia cells. Treatment with anti-Fas (7C11) monoclonal antibody (MoAb) induced apoptosis, evidenced by internucleosomal DNA fragmentation and propidium iodide staining, and was associated with increased expression of c-jun early response gene. We also show that anti-Fas MoAb treatment is associated with activation of stress-activated protein kinase (SAPK) and p38 mitogen-activated protein kinase (MAPK); however, no detectable increase in extracellular signal-regulated kinases (ERK1 and ERK2) activity was observed. Because interleukin-6 (IL-6) is a growth factor for MM cells and inhibits apoptosis induced by dexamethasone and serum starvation, we examined whether IL-6 affects anti-Fas MoAb-induced apoptosis and activation of SAPK or p38 MAPK in MM cells. Culture of MM cells with IL-6 before treatment with anti-Fas MoAb significantly reduced both DNA fragmentation and activation of SAPK, without altering induction of p38 MAPK activity. These results therefore suggest that anti-Fas MoAb-induced apoptosis in MM cells is associated with activation of SAPK, and that IL-6 may both inhibit apoptosis and modulate SAPK activity.
42
Chauhan, Dharminder, Surender Kharbanda, Atsushi Ogata, Mitsuyoshi Urashima, Gerrard Teoh, Michael Robertson, Donald W. Kufe i Kenneth C. Anderson. "Interleukin-6 Inhibits Fas-Induced Apoptosis and Stress-Activated Protein Kinase Activation in Multiple Myeloma Cells". Blood 89, nr 1 (1.01.1997): 227–34. http://dx.doi.org/10.1182/blood.v89.1.227.227_227_234.
Pełny tekst źródłaStreszczenie:
Fas belongs to the family of type-1 membrane proteins that transduce apoptotic signals. In the present studies, we characterized signaling during Fas-induced apoptosis in RPMI-8226 and IM-9 multiple myeloma (MM) derived cell lines as well as patient plasma cell leukemia cells. Treatment with anti-Fas (7C11) monoclonal antibody (MoAb) induced apoptosis, evidenced by internucleosomal DNA fragmentation and propidium iodide staining, and was associated with increased expression of c-jun early response gene. We also show that anti-Fas MoAb treatment is associated with activation of stress-activated protein kinase (SAPK) and p38 mitogen-activated protein kinase (MAPK); however, no detectable increase in extracellular signal-regulated kinases (ERK1 and ERK2) activity was observed. Because interleukin-6 (IL-6) is a growth factor for MM cells and inhibits apoptosis induced by dexamethasone and serum starvation, we examined whether IL-6 affects anti-Fas MoAb-induced apoptosis and activation of SAPK or p38 MAPK in MM cells. Culture of MM cells with IL-6 before treatment with anti-Fas MoAb significantly reduced both DNA fragmentation and activation of SAPK, without altering induction of p38 MAPK activity. These results therefore suggest that anti-Fas MoAb-induced apoptosis in MM cells is associated with activation of SAPK, and that IL-6 may both inhibit apoptosis and modulate SAPK activity.
43
Chakravortty, Dipshikha, Yutaka Kato, Tsuyoshi Sugiyama, Naoki Koide, Mya Mya Mu, Tomoaki Yoshida i Takashi Yokochi. "Inhibition of Caspase 3 Abrogates Lipopolysaccharide-Induced Nitric Oxide Production by Preventing Activation of NF-κB and c-Jun NH2-Terminal Kinase/Stress-Activated Protein Kinase in RAW 264.7 Murine Macrophage Cells". Infection and Immunity 69, nr 3 (1.03.2001): 1315–21. http://dx.doi.org/10.1128/iai.69.3.1315-1321.2001.
Pełny tekst źródłaStreszczenie:
ABSTRACT The effect of caspase inhibitors on lipopolysaccharide (LPS)-induced nitric oxide (NO) production in RAW 267.4 murine macrophage cells was investigated. Pretreatment of RAW cells with a broad caspase inhibitor, benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone (Z-VAD-FMK), resulted in a striking reduction in LPS-induced NO production. Z-VAD-FMK inhibited LPS-induced NF-κB activation. Furthermore, it blocked phosphorylation of c-Jun N-terminal kinase/stress-activated protein kinase (JNK/SAPK) but not that of extracellular signal-regulated kinase 1/2 and p38 mitogen-activated protein kinases. Similarly, a caspase 3-specific inhibitor, Z-Asp-Glu-Val-Asp-fluoromethylketone, inhibited NO production, NF-κB activation, and JNK/SAPK phosphorylation in LPS-stimulated RAW cells. The attenuated NO production was due to inhibition of the expression of an inducible-type NO synthase (iNOS). The overexpression of the dominant negative mutant of JNK/SAPK and the addition of a JNK/SAPK inhibitor blocked iNOS expression but did not block LPS-induced caspase 3 activation. It was therefore suggested that the inhibition of caspase 3 might abrogate LPS-induced NO production by preventing the activation of NF-κB and JNK/SAPK. The caspase family, especially caspase 3, is likely to play an important role in the signal transduction for iNOS-mediated NO production in LPS-stimulated mouse macrophages.
44
Nguyen, Hiep T., Rosalyn M. Adam, Samuel H. Bride, John M. Park, Craig A. Peters i Michael R. Freeman. "Cyclic stretch activates p38 SAPK2-, ErbB2-, and AT1-dependent signaling in bladder smooth muscle cells". American Journal of Physiology-Cell Physiology 279, nr 4 (1.10.2000): C1155—C1167. http://dx.doi.org/10.1152/ajpcell.2000.279.4.c1155.
Pełny tekst źródłaStreszczenie:
Cyclic mechanical stretch of bladder smooth muscle cells (SMC) increases rates of DNA synthesis and stimulates transcription of the gene for heparin-binding epidermal growth factor-like growth factor (HB-EGF), an ErbB1/EGF receptor ligand that has been linked to hypertrophic bladder growth. In this study we sought to clarify the signaling pathways responsible for mechanotransduction of the stretch stimulus. HB-EGF mRNA levels, DNA synthesis, and AP-1/Ets DNA binding activities were induced by repetitive stretch of primary culture rat bladder SMC. Inhibitors of the p38 SAPK2 pathway, the angiotensin receptor type 1 (AT1), and the ErbB2 tyrosine kinase reduced each of these activities, while an inhibitor of the extracellular signal-regulated kinase mitogen-activated protein kinase (Erk-MAPK) pathway had no effect. Stretch rapidly activated stress-activated protein kinase 2 (p38 SAPK2) and Jun NH2-terminal kinase (JNK)/SAPK pathways but not the Erk-MAPK pathway and induced ErbB2 but not ErbB1 phosphorylation. Angiotensin II (ANG II) a bladder SMC mitogen previously linked to the stretch response, did not activate ErbB2, and ErbB2 activation occurred in response to stretch in the presence of an ANG receptor inhibitor, indicating that activation of the AT1-mediated pathway and the ErbB2-dependent pathway occurs by independent mechanisms. p38 SAPK2 and JNK/SAPK signaling also appeared to be independent of the ErbB2 and AT1 pathways. These findings indicate that stretch-stimulated DNA synthesis and gene expression in normal bladder SMC occur via multiple independent receptor systems (e.g., AT1 and ErbB2) and at least one MAPK pathway (p38 SAPK2). Further, we show that the Erk-MAPK pathway, which in most systems is linked to receptor-dependent cell growth responses, is not involved in progression to DNA synthesis or in the response of the HB-EGF gene to mechanical forces.
45
Taylor, Brad N., Peter Staib, Ayfer Binder, Antje Biesemeier, Miriam Sehnal, Martin Röllinghoff, Joachim Morschhäuser i Klaus Schröppel. "Profile of Candida albicans-Secreted Aspartic Proteinase Elicited during Vaginal Infection". Infection and Immunity 73, nr 3 (marzec 2005): 1828–35. http://dx.doi.org/10.1128/iai.73.3.1828-1835.2005.
Pełny tekst źródłaStreszczenie:
ABSTRACT Vaginal infections caused by the opportunistic yeast Candida albicans are a significant problem in women of child-bearing age. Several factors are recognized as playing a crucial role in the pathogenesis of superficial candidiasis; these factors include hyphal formation, phenotypic switching, and the expression of virulence factors, including a 10-member family of secreted aspartic proteinases. In the present investigation, we analyzed the secreted aspartic proteinase gene (SAP) expression profile of C. albicans that is elicited in the course of vaginal infection in mice and how this in vivo expression profile is associated with hyphal formation. We utilized two different genetic reporter systems that allowed us to observe SAP expression on a single-cell basis, a recombination-based in vivo expression technology and green fluorescent protein-expressing Candida reporter strains. Of the six SAP genes that were analyzed (SAP1 to SAP6), only SAP4 and SAP5 were detectably induced during infection in this model. Expression of both of these genes was associated with hyphal growth, although not all hyphal cells detectably expressed SAP4 and SAP5. SAP5 expression was induced soon after infection, whereas SAP4 was expressed at later times and in fewer cells compared with SAP5. These findings point to a link between morphogenetic development and expression of virulence genes during Candida vaginitis in mice, where host signals induce both hyphal formation and expression of SAP4 and SAP5, but temporal gene expression patterns are ultimately controlled by other factors.
46
Stiefel, Jeffrey, Lili Wang, David A. Kelly, Rozmin T. K. Janoo, Jeffrey Seitz, Simon K. Whitehall i Charles S. Hoffman. "Suppressors of an Adenylate Cyclase Deletion in the Fission Yeast Schizosaccharomyces pombe". Eukaryotic Cell 3, nr 3 (czerwiec 2004): 610–19. http://dx.doi.org/10.1128/ec.3.3.610-619.2004.
Pełny tekst źródłaStreszczenie:
ABSTRACT Schizosaccharomyces pombe utilizes two opposing signaling pathways to sense and respond to its nutritional environment. Glucose detection triggers a cyclic AMP signal to activate protein kinase A (PKA), while glucose or nitrogen starvation activates the Spc1/Sty1 stress-activated protein kinase (SAPK). One process controlled by these pathways is fbp1 + transcription, which is glucose repressed. In this study, we isolated strains carrying mutations that reduce high-level fbp1 + transcription conferred by the loss of adenylate cyclase (git2Δ), including both wis1 − (SAPK kinase) and spc1 − (SAPK) mutants. While characterizing the git2Δ suppressor strains, we found that the git2Δ parental strains are KCl sensitive, though not osmotically sensitive. Of 102 git2Δ suppressor strains, 17 strains display KCl-resistant growth and comprise a single linkage group, carrying mutations in the cgs1 + PKA regulatory subunit gene. Surprisingly, some of these mutants are mostly wild type for mating and stationary-phase viability, unlike the previously characterized cgs1-1 mutant, while showing a significant defect in fbp1-lacZ expression. Thus, certain cgs1 − mutant alleles dramatically affect some PKA-regulated processes while having little effect on others. We demonstrate that the PKA and SAPK pathways regulate both cgs1 + and pka1 + transcription, providing a mechanism for cross talk between these two antagonistically acting pathways and feedback regulation of the PKA pathway. Finally, strains defective in both the PKA and SAPK pathways display transcriptional regulation of cgs1 + and pka1 +, suggesting the presence of a third glucose-responsive signaling pathway.
47
Pietrella, Donatella, Anna Rachini, Neelam Pandey, Lydia Schild, Mihai Netea, Francesco Bistoni, Bernhard Hube i Anna Vecchiarelli. "The Inflammatory Response Induced by Aspartic Proteases of Candida albicans Is Independent of Proteolytic Activity". Infection and Immunity 78, nr 11 (16.08.2010): 4754–62. http://dx.doi.org/10.1128/iai.00789-10.
Pełny tekst źródłaStreszczenie:
ABSTRACT The secretion of aspartic proteases (Saps) has long been recognized as a virulence-associated trait of the pathogenic yeast Candida albicans. In this study, we report that different recombinant Saps, including Sap1, Sap2, Sap3, and Sap6, have differing abilities to induce secretion of proinflammatory cytokines by human monocytes. In particular Sap1, Sap2, and Sap6 significantly induced interleukin-1β (IL-1β), tumor necrosis factor alpha (TNF-α), and IL-6 production. Sap3 was able to stimulate the secretion of IL-1β and TNF-α. All Saps tested were able to induce Ca2+ influx in monocytes. Treatment of these Saps with pepstatin A did not have any effect on cytokine secretion, indicating that their stimulatory potential was independent from their proteolytic activity. The capacity of Saps to induce inflammatory cytokine production was also independent from protease-activated receptor (PAR) activation and from the optimal pH for individual Sap activity. The interaction of Saps with monocytes induced Akt activation and phosphorylation of IκBα, which mediates translocation of NF-κB into the nucleus. Overall, these results suggest that individual Sap proteins can induce an inflammatory response and that this phenomenon is independent from the pH of a specific host niche and from Sap enzymatic activity. The inflammatory response is partially dependent on Sap denaturation and is triggered by the Akt/NF-κB activation pathway. Our data suggest a novel, activity-independent aspect of Saps during interactions of C. albicans with the host.
48
Foltz, Ian N., i John W. Schrader. "Activation of the Stress-Activated Protein Kinases by Multiple Hematopoietic Growth Factors With the Exception of Interleukin-4". Blood 89, nr 9 (1.05.1997): 3092–96. http://dx.doi.org/10.1182/blood.v89.9.3092.
Pełny tekst źródłaStreszczenie:
Abstract The stress-activated protein/c-Jun N-terminal kinases (SAPK/JNK) have been shown to be activated by pro-inflammatory cytokines, as well as physical and chemical stresses. We now show that a variety of hematopoietic growth factors, including Steel locus factor (SLF ), granulocyte-macrophage colony-stimulating factor (GM-CSF ), and interleukin-3 (IL-3), all of which promote the growth and survival of various lineages of hematopoietic cells, activate the stress-activated protein kinases in the factor-dependent cell line MC/9. These hematopoietic growth factors activated both 46- and 55-kD isoforms of both SAPKγ and SAPKα. Furthermore, we demonstrate that SAPK activation correlated with the phosphorylation of SAPK/ERK kinase-1 (SEK1) after treatment with SLF or GM-CSF. Interestingly, IL-4, a cytokine with distinctive and important effects on the immune system, was the exception among the hematopoietic growth factors we examined in failing to induce activation of SAPKγ, SAPKα, or SEK1. These findings show that activation of SAPK is involved, not only in responses to stresses, but also in signaling by growth factors that regulate the normal development and function of cells of the immune system.
49
STANISZEWSKA, MONIKA, MAŁGORZATA BONDARYK, TADEUSZ MALEWSKI i WIESŁAW KURZĄTKOWSKI. "Quantitative Expression of the Candida albicans Aspartyl Proteinase Genes SAP7, SAP8, SAP9, SAP10 in Human Serum in vitro". Polish Journal of Microbiology 63, nr 1 (2014): 15–20. http://dx.doi.org/10.33073/pjm-2014-002.
Pełny tekst źródłaStreszczenie:
The different members of the secreted aspartyl proteinase (Sap) family of the human pathogenic yeast Candida albicans are proposed to play different roles during infection and are differentially expressed at various body sites. In recent reports, expression analysis has focused on the genes SAP1-6, while the expression pattern of SAP7-10 was less well studied. We analyzed the SAP7-SAP10 expression profile of C. albicans under human serum influence that may be elucidated in the course of blood infection in humans and how this in vitro expression profile is associated with hyphal formation. The phenotypes of strains were examined under scanning electron microscopy. Quantitative RT-PCR (2-(deltadeltaC)T) was used to monitor SAP expression of C. albicans wild type cells and mutants lacking SAP9 and/or SAP10. Of the four analyzed SAP genes, only SAP7 was detectably induced in the double mutant and in the wild type strains in the model that mimics bloodstream infections. On the other hand, in the wild types (isolate 83 and CAF2-1), SAP7 was expressed 0.8- or 0.4-fold less than SAP10, respectively. Our findings suggest that Sap7 may respond to the challenge of the human blood environment. Furthermore, the results support the notion that compensatory upregulation of SAP7 and SAP8 in the deltasap9/deltasap10 mutant occurs in these conditions. SAP7-10 expression was strain-specific. Our findings point to a link between morphogenesis and expression of SAP9 in serum, where these conditions induce both hyphae and SAP9, but temporal gene expression patterns might be controlled by other factors.
50
Nishina, Hiroshi, Martin Bachmann, Antonio J. Oliveira-dos-Santos, Ivona Kozieradzki, Klaus D. Fischer, Bernhard Odermatt, Andrew Wakeham i in. "Impaired CD28-mediated Interleukin 2 Production and Proliferation in Stress Kinase SAPK/ERK1 Kinase (SEK1)/Mitogen-activated Protein Kinase Kinase 4 (MKK4)-deficient T Lymphocytes". Journal of Experimental Medicine 186, nr 6 (15.09.1997): 941–53. http://dx.doi.org/10.1084/jem.186.6.941.
Pełny tekst źródłaStreszczenie:
The dual specific kinase SAPK/ERK1 kinase (SEK1; mitogen-activated protein kinase kinase 4/Jun NH2 terminal kinase [ JNK] kinase) is a direct activator of stress-activated protein kinases ([SAPKs]/JNKs) in response to CD28 costimulation, CD40 signaling, or activation of the germinal center kinase. Here we show that SEK1−/− recombination-activating gene (RAG)2−/− chimeric mice have a partial block in B cell maturation. However, peripheral B cells displayed normal responses to IL-4, IgM, and CD40 cross-linking. SEK1−/− peripheral T cells showed decreased proliferation and IL-2 production after CD28 costimulation and PMA/Ca2+ ionophore activation. Although CD28 expression was absolutely crucial to generate vesicular stomatitis virus (VSV)-specific germinal centers, SEK1−/−RAG2−/− chimeras mounted a protective antiviral B cell response, exhibited normal IgG class switching, and made germinal centers in response to VSV. Interestingly, PMA/Ca2+ ionophore stimulation, which mimics TCR–CD3 and CD28-mediated signal transduction, induced SAPK/JNK activation in peripheral T cells, but not in thymocytes, from SEK1−/− mice. These results show that signaling pathways for SAPK activation are developmentally regulated in T cells. Although SEK1−/− thymocytes failed to induce SAPK/JNK in response to PMA/Ca2+ ionophore, SEK1−/−RAG2−/− thymocytes proliferated and made IL-2 after PMA/Ca2+ ionophore and CD3/CD28 stimulation, albeit at significantly lower levels compared to SEK1+/+RAG2−/− thymocytes, implying that CD28 costimulation and PMA/Ca2+ ionophore–triggered signaling pathways exist that can mediate proliferation and IL-2 production independently of SAPK activation. Our data provide the first genetic evidence that SEK1 is an important effector molecule that relays CD28 signaling to IL-2 production and T cell proliferation.