Relevant bibliographies by topics / SgK269 / Journal articles

Journal articles on the topic 'SgK269'

To see the other types of publications on this topic, follow the link: SgK269.
Author: Grafiati
Published: 10 December 2022
Last updated: 28 January 2023

Create a spot-on reference in APA, MLA, Chicago, Harvard, and other styles

Select a source type:

Consult the top 50 journal articles for your research on the topic 'SgK269.'

Next to every source in the list of references, there is an 'Add to bibliography' button. Press on it, and we will generate automatically the bibliographic reference to the chosen work in the citation style you need: APA, MLA, Harvard, Chicago, Vancouver, etc.

You can also download the full text of the academic publication as pdf and read online its abstract whenever available in the metadata.

Browse journal articles on a wide variety of disciplines and organise your bibliography correctly.

1

O'Rourke, Rachelle L., and Roger J. Daly. "The pseudokinases SgK269 and SgK223: A novel oncogenic alliance in human cancer." Cell Adhesion & Migration 12, no. 6 (December 21, 2017): 524–28. http://dx.doi.org/10.1080/19336918.2017.1394570.

Full text
APA, Harvard, Vancouver, ISO, and other styles
2

Liu, Ling, Yu Wei Phua, Rachel S. Lee, Xiuquan Ma, Yiping Jenkins, Karel Novy, Emily S. Humphrey, et al. "Homo- and Heterotypic Association Regulates Signaling by the SgK269/PEAK1 and SgK223 Pseudokinases." Journal of Biological Chemistry 291, no. 41 (August 16, 2016): 21571–83. http://dx.doi.org/10.1074/jbc.m116.748897.

Full text
APA, Harvard, Vancouver, ISO, and other styles
3

Lopez, Mitchell L., Megan Lo, Jennifer E. Kung, Małgorzata Dudkiewicz, Gwendolyn M. Jang, John Von Dollen, Jeffrey R. Johnson, Nevan J. Krogan, Krzysztof Pawłowski, and Natalia Jura. "PEAK3/C19orf35 pseudokinase, a new NFK3 kinase family member, inhibits CrkII through dimerization." Proceedings of the National Academy of Sciences 116, no. 31 (July 16, 2019): 15495–504. http://dx.doi.org/10.1073/pnas.1906360116.

Full text
Abstract:
Members of the New Kinase Family 3 (NKF3), PEAK1/SgK269 and Pragmin/SgK223 pseudokinases, have emerged as important regulators of cell motility and cancer progression. Here, we demonstrate that C19orf35 (PEAK3), a newly identified member of the NKF3 family, is a kinase-like protein evolutionarily conserved across mammals and birds and a regulator of cell motility. In contrast to its family members, which promote cell elongation when overexpressed in cells, PEAK3 overexpression does not have an elongating effect on cell shape but instead is associated with loss of actin filaments. Through an unbiased search for PEAK3 binding partners, we identified several regulators of cell motility, including the adaptor protein CrkII. We show that by binding to CrkII, PEAK3 prevents the formation of CrkII-dependent membrane ruffling. This function of PEAK3 is reliant upon its dimerization, which is mediated through a split helical dimerization domain conserved among all NKF3 family members. Disruption of the conserved DFG motif in the PEAK3 pseudokinase domain also interferes with its ability to dimerize and subsequently bind CrkII, suggesting that the conformation of the pseudokinase domain might play an important role in PEAK3 signaling. Hence, our data identify PEAK3 as an NKF3 family member with a unique role in cell motility driven by dimerization of its pseudokinase domain.
APA, Harvard, Vancouver, ISO, and other styles
4

Croucher, David R., Falko Hochgräfe, Luxi Zhang, Ling Liu, Ruth J. Lyons, Danny Rickwood, Carole M. Tactacan, et al. "Involvement of Lyn and the Atypical Kinase SgK269/PEAK1 in a Basal Breast Cancer Signaling Pathway." Cancer Research 73, no. 6 (February 1, 2013): 1969–80. http://dx.doi.org/10.1158/0008-5472.can-12-1472.

Full text
APA, Harvard, Vancouver, ISO, and other styles
5

Yoshida-Moriguchi, Takako, Tobias Willer, Mary E. Anderson, David Venzke, Tamieka Whyte, Francesco Muntoni, Hane Lee, Stanley F. Nelson, Liping Yu, and Kevin P. Campbell. "SGK196 Is a Glycosylation-Specific O-Mannose Kinase Required for Dystroglycan Function." Science 341, no. 6148 (August 8, 2013): 896–99. http://dx.doi.org/10.1126/science.1239951.

Full text
Abstract:
Phosphorylated O-mannosyl trisaccharide [N-acetylgalactosamine–β3-N-acetylglucosamine–β4-(phosphate-6-)mannose] is required for dystroglycan to bind laminin-G domain–containing extracellular proteins with high affinity in muscle and brain. However, the enzymes that produce this structure have not been fully elucidated. We found that glycosyltransferase-like domain–containing 2 (GTDC2) is a protein O-linked mannose β 1,4-N-acetylglucosaminyltransferase whose product could be extended by β 1,3-N-acetylgalactosaminyltransferase2 (B3GALNT2) to form the O-mannosyl trisaccharide. Furthermore, we identified SGK196 as an atypical kinase that phosphorylated the 6-position of O-mannose, specifically after the mannose had been modified by both GTDC2 and B3GALNT2. These findings suggest how mutations in GTDC2, B3GALNT2, and SGK196 disrupt dystroglycan receptor function and lead to congenital muscular dystrophy.
APA, Harvard, Vancouver, ISO, and other styles
6

Pao, Alan C., Aditi Bhargava, Francesca Di Sole, Raymond Quigley, Xinli Shao, Jian Wang, Sheela Thomas, et al. "Expression and role of serum and glucocorticoid-regulated kinase 2 in the regulation of Na+/H+ exchanger 3 in the mammalian kidney." American Journal of Physiology-Renal Physiology 299, no. 6 (December 2010): F1496—F1506. http://dx.doi.org/10.1152/ajprenal.00075.2010.

Full text
Abstract:
Serum and glucocorticoid-regulated kinase 2 (sgk2) is 80% identical to the kinase domain of sgk1, an important mediator of mineralocorticoid-regulated sodium (Na+) transport in the distal nephron of the kidney. The expression pattern and role in renal function of sgk2 are virtually uncharacterized. In situ hybridization and immunohistochemistry of rodent kidney coupled with real-time RT-PCR of microdissected rat kidney tubules showed robust sgk2 expression in the proximal straight tubule and thick ascending limb of the loop of Henle. Sgk2 expression was minimal in distal tubule cells with aquaporin-2 immunostaining but significant in proximal tubule cells with Na+/H+ exchanger 3 (NHE3) immunostaining. To ascertain whether mineralocorticoids regulate expression of sgk2 in a manner similar to sgk1, we examined sgk2 mRNA expression in the kidneys of adrenalectomized rats treated with physiological doses of aldosterone together with the glucocorticoid receptor antagonist RU486. Northern blot analysis and in situ hybridization showed that, unlike sgk1, sgk2 expression in the kidney was not altered by aldosterone treatment. Based on the observation that sgk2 is expressed in proximal tubule cells that also express NHE3, we asked whether sgk2 regulates NHE3 activity. We heterologously expressed sgk2 in opossum kidney (OKP) cells and measured Na+/H+ exchange activity by Na+-dependent cell pH recovery. Constitutively active sgk2, but not sgk1, stimulated Na+/H+ exchange activity by >30%. Moreover, the sgk2-mediated increase in Na+/H+ exchange activity correlated with an increase in cell surface expression of NHE3. Together, these results suggest that the pattern of expression, regulation, and role of sgk2 within the mammalian kidney are distinct from sgk1 and that sgk2 may play a previously unrecognized role in the control of transtubular Na+ transport through NHE3 in the proximal tubule.
APA, Harvard, Vancouver, ISO, and other styles
7

Ranzuglia, Valentina, Ilaria Lorenzon, Ilenia Pellarin, Maura Sonego, Alessandra Dall’Acqua, Sara D’Andrea, Sara Lovisa, et al. "Serum- and glucocorticoid- inducible kinase 2, SGK2, is a novel autophagy regulator and modulates platinum drugs response in cancer cells." Oncogene 39, no. 40 (August 27, 2020): 6370–86. http://dx.doi.org/10.1038/s41388-020-01433-6.

Full text
Abstract:
Abstract For many tumor types chemotherapy still represents the therapy of choice and many standard treatments are based on the use of platinum (PT) drugs. However, de novo or acquired resistance to platinum is frequent and leads to disease progression. In Epithelial Ovarian Cancer (EOC) patients, PT-resistant recurrences are very common and improving the response to treatment still represents an unmet clinical need. To identify new modulators of PT-sensitivity, we performed a loss-of-function screening targeting 680 genes potentially involved in the response of EOC cells to platinum. We found that SGK2 (Serum-and Glucocorticoid-inducible kinase 2) plays a key role in PT-response. We show here that EOC cells relay on the induction of autophagy to escape PT-induced death and that SGK2 inhibition increases PT sensitivity inducing a block in the autophagy cascade due to the impairment of lysosomal acidification. Mechanistically we demonstrate that SGK2 controls autophagy in a kinase-dependent manner by binding and inhibiting the V-ATPase proton pump. Accordingly, SGK2 phosphorylates the subunit V1H (ATP6V1H) of V-ATPase and silencing or chemical inhibition of SGK2, affects the normal autophagic flux and sensitizes EOC cells to platinum. Hence, we identified a new pathway that links autophagy to the survival of cancer cells under platinum treatment in which the druggable kinase SGK2 plays a central role. Our data suggest that blocking autophagy via SGK2 inhibition could represent a novel therapeutic strategy to improve patients’ response to platinum.
APA, Harvard, Vancouver, ISO, and other styles
8

KOBAYASHI, Takayasu, Maria DEAK, Nick MORRICE, and Philip COHEN. "Characterization of the structure and regulation of two novel isoforms of serum- and glucocorticoid-induced protein kinase." Biochemical Journal 344, no. 1 (November 8, 1999): 189–97. http://dx.doi.org/10.1042/bj3440189.

Full text
Abstract:
The catalytic domain of serum- and glucocorticoid-induced protein kinase (SGK) is 54% identical with protein kinase B (PKB) and, like PKB, is activated in vitro by 3-phosphoinositide-dependent protein kinase-1 (PDK1) and in vivo in response to signals that activate phosphatidylinositol (PI) 3-kinase. Here we identify two novel isoforms of SGK, termed SGK2 and SGK3, whose catalytic domains share 80% amino acid sequence identity with each other and with SGK (renamed SGK1). Like SGK1, the mRNA encoding SGK3 is expressed in all tissues examined, but SGK2 mRNA is only present at significant levels in liver, kidney and pancreas and, at lower levels, in the brain. The levels of SGK2 mRNA in H4IIE cells and SGK3 mRNA in Rat2 fibroblasts are not increased by stimulation with serum or dexamethasone, whereas the level of SGK1 mRNA is increased greatly. SGK2 and SGK3 are activated in vitro by PDK1, albeit more slowly than SGK1, and their activation is accompanied by the phosphorylation of Thr193 and Thr253 respectively, the residues equivalent to the Thr in the ‘activation loop’ of PKB that is targeted by PDK1. The PDK1-catalysed phosphorylation and activation of SGK2 and SGK3, like SGK1, is greatly potentiated by mutating Ser356 and Ser419 respectively to Asp, these residues being equivalent to the C-terminal phosphorylation site of PKB. Like SGK1, SGK2 and SGK3 are activated 5-fold via a phosphorylation mechanism when cells are exposed to H2O2 but, in contrast with SGK1, activation is only suppressed partially by inhibitors of PI 3-kinase. SGK2 and SGK3 are activated to a smaller extent by insulin-like growth factor-1 (2-fold) than SGK1 (5-fold). Like PKB and SGK1, SGK2 and SGK3 preferentially phosphorylate Ser and Thr residues that lie in Arg-Xaa-Arg-Xaa-Xaa-Ser/Thr motifs.
APA, Harvard, Vancouver, ISO, and other styles
9

Ardicli, D., R. Gocmen, S. Cirak, B. Talim, G. Haliloglu, and H. Topaloglu. "Congenital mirror movements in alpha-dystroglycanopathy (ADG) due to SGK196 mutation." Neuromuscular Disorders 26 (October 2016): S165. http://dx.doi.org/10.1016/j.nmd.2016.06.287.

Full text
APA, Harvard, Vancouver, ISO, and other styles
10

He, Peijian, Sei-Jung Lee, Songbai Lin, Ursula Seidler, Florian Lang, Geza Fejes-Toth, Aniko Naray-Fejes-Toth, and C. Chris Yun. "Serum- and glucocorticoid-induced kinase 3 in recycling endosomes mediates acute activation of Na+/H+ exchanger NHE3 by glucocorticoids." Molecular Biology of the Cell 22, no. 20 (October 15, 2011): 3812–25. http://dx.doi.org/10.1091/mbc.e11-04-0328.

Full text
Abstract:
Na+/H+ exchanger 3 (NHE3) is the major Na+ transporter in the intestine. Serum- and glucocorticoid-induced kinase (SGK) 1 interacts with NHE regulatory factor 2 (NHERF2) and mediates activation of NHE3 by dexamethasone (Dex) in cultured epithelial cells. In this study, we compared short-term regulation of NHE3 by Dex in SGK1-null and NHERF2-null mice. In comparison to wild-type mice, loss of SGK1 or NHERF2 significantly attenuated regulation of NHE3 by Dex but did not completely obliterate the effect. We show that transfection of SGK2 or SGK3 in PS120 cells resulted in robust activation of NHE3 by Dex. However, unlike SGK1 or SGK2, SGK3 rapidly activated NHE3 within 15 min of Dex treatment in both PS120 and Caco-2bbe cells. Immunofluorescence analysis showed that SGK3 colocalized with NHE3 in recycling endosomes, whereas SGK1 and SGK2 were diffusely distributed. Mutation of Arg-90 of SGK3 disrupted the endosomal localization of SGK3 and delayed NHE3 activation. Activation of SGK3 and NHE3 by Dex was dependent on phosphoinositide 3-kinase (PI3K) and phosphoinositide-dependent kinase 1 (PDK1), and Dex induced translocation of PDK1 to endosomes. Our study identifies SGK3 as a novel endosomal kinase that acutely regulates NHE3 in a PI3K-dependent mechanism.
APA, Harvard, Vancouver, ISO, and other styles
11

Glenn, Martha J., Rosalie G. Waller, and Nicola J. Camp. "Exome Sequencing in a Family with Chronic Lymphocytic Leukemia, Mantle Cell Lymphoma and Autoimmune Disease Uncovers Potential Germline Risk-Alleles." Blood 124, no. 21 (December 6, 2014): 5629. http://dx.doi.org/10.1182/blood.v124.21.5629.5629.

Full text
Abstract:
Abstract We identified a Caucasian family with dense distribution of B-cell non-Hodgkin lymphoma (NHL) and autoimmune disease (Figure 1). Within the family, three siblings and their mother have B-cell NHL (three with chronic lymphocytic leukemia [CLL]; one with mantle cell lymphoma [MCL]), and four family members have autoimmune diseases (rheumatoid arthritis or multiple sclerosis). In addition, two family members have melanoma. To investigate the genetic factors involved in B-cell NHL in this family, we exome sequenced nine individuals, including two unaffected spouses as technical-artifact controls. Following best-practice guidelines, we performed joint variant calling, including an additional 135 European 1000Genome exomes as a set of background controls. Figure 1 Figure 1. After variant quality control, a total of 676,137 sequence variants were identified. We also performed individual genotype quality control based on a minimum read depth of 10 and genotype quality of 40, resulting in 554,690 variants. For our initial prioritization, we required that variants be: absent in the spouse controls, have minor allele frequency (MAF) ≤ 0.05 in the 1000Genome exomes, and be shared by all four B-cell NHL cases. This resulted in 73 variants of potential interest. Of the 73 variants, seven were predicted to be damaging by either PROVEAN or SIFT, two by both algorithms and by PolyPhen2. These two potentially damaging variants reside in the genes CCDC144A and RRS1. The gene CCDC144A is located at chromosome 17p11.2, a known breakpoint region of the 17p deletion often seen in CLL tumor cells. The variant identified in this gene was rare (MAF = 0.001 in the NHLBI Exome Sequencing Project [ESP]) and was also seen in two additional family members (one with rheumatoid arthritis; a second with rheumatoid arthritis and melanoma). The gene RRS1 is located at chromosome 8q13.1, and has been shown to be important for proper chromosomal organization during mitosis. The variant identified in this gene was relatively rare (MAF = 0.041 in ESP) and was seen in the same, two additional family members. Of the remaining five variants predicted damaging by only one algorithm, of interest were two variants in the SGK223 gene on chromosome 8p23.1. SGK223 is a kinase and a component in the BCR-ABL1 signaling network that is present in most chronic myelogenous leukemia cases and a quarter of adult acute lymphoblastic leukemia cases. Both of the variants in SGK223 were also seen in three additional family members (one with rheumatoid arthritis; a second with rheumatoid arthritis and melanoma; a third with melanoma). In addition to prioritization by predicted function of coding variants, we explored the 73 variants for overlap with findings from published germ-line investigations of B-cell NHL. This identified one variant in the ACOXL gene at chromosome 2q13. The variant is relatively rare (MAF = 0.017 in dbSNP) and lies in the same gene and intron (17,016 base pairs upstream) as rs13401811, the associated SNP (p = 2.08 x 10-18) reported in a genomewide association study (GWAS) for CLL. Our ongoing analyses and prioritization of the variants in this extraordinary family reveal overlap with signals coming from GWAS studies and suggest some potentially damaging variants in genes not previously implicated in NHL. The potential risk-alleles identified in our preliminary findings could shed new light about the genes and genetic factors involved in NHL. Disclosures No relevant conflicts of interest to declare.
APA, Harvard, Vancouver, ISO, and other styles
12

Zhou, Nannan, Bo Ding, Michele Agler, Mark Cockett, and Fiona McPhee. "Lethality of PAK3 and SGK2 shRNAs to Human Papillomavirus Positive Cervical Cancer Cells Is Independent of PAK3 and SGK2 Knockdown." PLOS ONE 10, no. 1 (January 23, 2015): e0117357. http://dx.doi.org/10.1371/journal.pone.0117357.

Full text
APA, Harvard, Vancouver, ISO, and other styles
13

Kim, Jeongeun, Donghee Kim, Hyunho Jung, Jinho Lee, and Victor Sukbong Hong. "Identification and Kinetic Characterization of Serum- and Glucocorticoid-Regulated Kinase Inhibitors Using a Fluorescence Polarization–Based Assay." SLAS DISCOVERY: Advancing the Science of Drug Discovery 26, no. 5 (March 30, 2021): 655–62. http://dx.doi.org/10.1177/24725552211002465.

Full text
Abstract:
The serum- and glucocorticoid-regulated kinase (SGK) family consists of three isoforms (SGK1, SGK2, and SGK3) that have been implicated in the regulation of tumor growth, metastasis, autophagy, and epithelial ion transport. SGK1 and SGK3 play essential roles in protein kinase B (AKT or PKB)-independent phosphoinositide 3-kinases (PI3K)-mediated tumorigenesis, as evidenced by the significantly elevated expression levels of SGK1 and SGK3 in many cancers, including prostate cancer, colorectal carcinoma, estrogen-dependent breast cancer, and glioblastoma. Therefore, SGK is a potential target for anticancer therapy. A small kinase-focused library comprising 160 compounds was screened against SGK1 using a fluorescence polarization–based kinase assay that yielded a Z’-factor of 0.82. Among the 39 compounds obtained as initial hits in a primary screen, 12 compounds contained the thiazolidine-2,4-dione scaffold. The inhibitory mechanisms of the most potent hit, KMU010402, were further investigated using kinetic analyses, followed by determination of the inhibition constants for SGK1, SGK2, and SGK3. Molecular modeling was used to propose a potential binding mode of KMU010402 to SGK1.
APA, Harvard, Vancouver, ISO, and other styles
14

Bilanges, Benoit, and Bart Vanhaesebroeck. "Cinderella finds her shoe: the first Vps34 inhibitor uncovers a new PI3K–AGC protein kinase connection." Biochemical Journal 464, no. 2 (November 14, 2014): e7-e10. http://dx.doi.org/10.1042/bj20141218.

Full text
Abstract:
Class II/III PI3Ks (phosphoinositide 3-kinases) produce the PtdIns(3)P lipid that is involved in intracellular vesicular trafficking. In contrast with class I PI3Ks, the potential signalling roles of class II/III PI3Ks are poorly understood. In a recent article in the Biochemical Journal, Bago and co-workers report that Vps34 (vacuolar protein sorting 34), the only class III PI3K, controls the activity of SGK3 (serum- and glucocorticoid-regulated protein kinase 3). Like other AGC kinases, the SGKs (SGK1, SGK2 and SGK3) are activated by dual phosphorylation. Unlike its cousins SGK1 and SGK2, SGK3 contains a PtdIns(3)P-binding domain, providing an additional element of regulation. The study by Bago et al. characterizes and makes extensive use of a Novartis Vps34 inhibitor (VPS34-IN1) that inhibits this PI3K isoform with nanomolar potency, without affecting other lipid kinases or more than 300 protein kinases. The authors show that this compound very rapidly reduced PtdIns(3)P levels at the endosome with concomitant loss of SGK3 phosphorylation. Co-inhibition of class I PI3Ks led to a further reduction in SGK3 activity, indicating that class I PI3Ks may also regulate SGK3 activity through an additional, currently unknown, mechanism. It remains to be assessed whether the novel PI3K–protein kinase connection established by this study is subject to acute cellular stimulation or is part of a constitutive housekeeping function. VPS34-IN1 will provide a useful tool to decipher the kinase-dependent functions of Vps34, with acute changes in SGK3 phosphorylation and subcellular localization being new biomarkers of Vps34 activity.
APA, Harvard, Vancouver, ISO, and other styles
15

Pao, Alan C., James A. McCormick, Hongyan Li, John Siu, Cedric Govaerts, Vivek Bhalla, Rama Soundararajan, and David Pearce. "NH2 terminus of serum and glucocorticoid-regulated kinase 1 binds to phosphoinositides and is essential for isoform-specific physiological functions." American Journal of Physiology-Renal Physiology 292, no. 6 (June 2007): F1741—F1750. http://dx.doi.org/10.1152/ajprenal.00027.2007.

Full text
Abstract:
Serum and glucocorticoid regulated kinase 1 (SGK1) has been identified as a key regulatory protein that controls a diverse set of cellular processes including sodium (Na+) homeostasis, osmoregulation, cell survival, and cell proliferation. Two other SGK isoforms, SGK2 and SGK3, have been identified, which differ most markedly from SGK1 in their NH2-terminal domains. We found that SGK1 and SGK3 are potent stimulators of epithelial Na+ channel (ENaC)-dependent Na+ transport, while SGK2, which has a short NH2 terminus, is a weak stimulator of ENaC. Further characterization of the role of the SGK1 NH2 terminus revealed that its deletion does not affect in vitro kinase activity but profoundly limits the ability of SGK1 either to stimulate ENaC-dependent Na+ transport or inhibit Forkhead-dependent gene transcription. The NH2 terminus of SGK1, which shares sequence homology with the phosphoinositide 3-phosphate [PI( 3 )P] binding domain of SGK3, binds phosphoinositides in protein lipid overlay assays, interacting specifically with PI( 3 )P, PI( 4 )P, and PI( 5 )P, but not with PI( 3 , 4 , 5 )P3. Moreover, a point mutation that reduces phosphoinositide binding to the NH2 terminus also reduces SGK1 effects on Na+ transport and Forkhead activity. These data suggest that the NH2 terminus, although not required for PI 3-kinase-dependent modulation of SGK1 catalytic activity, is required for multiple SGK1 functions, including stimulation of ENaC and inhibition of the proapoptotic Forkhead transcription factor. Together, these observations support the idea that the NH2-terminal domain acts downstream of PI 3-kinase-dependent activation to target the kinase to specific cellular compartments and/or substrates, possibly through its interactions with a subset of phosphoinositides.
APA, Harvard, Vancouver, ISO, and other styles
16

Cicenas, Jonas, Edita Meskinyte-Kausiliene, Vigilijus Jukna, Arnas Rimkus, Jokubas Simkus, and Diana Soderholm. "SGK1 in Cancer: Biomarker and Drug Target." Cancers 14, no. 10 (May 12, 2022): 2385. http://dx.doi.org/10.3390/cancers14102385.

Full text
Abstract:
Serum- and glucocorticoid-regulated kinases (SGKs) are members of the AGC family of serine/threonine kinases, consisting of three isoforms: SGK1, SGK2, and SGK3. SGK1 was initially cloned as a gene transcriptionally stimulated by serum and glucocorticoids in rat mammary tumor cells. It is upregulated in some cancers and downregulated in others. SGK1 increases tumor cell survival, adhesiveness, invasiveness, motility, and epithelial to mesenchymal transition. It stimulates tumor growth by mechanisms such as activation of K+ channels and Ca2+ channels, Na+/H+ exchanger, amino acid and glucose transporters, downregulation of Foxo3a and p53, and upregulation of β-catenin and NFκB. This chapter focuses on major aspects of SGK1 involvement in cancer, its use as biomarker as well as potential therapeutic target.
APA, Harvard, Vancouver, ISO, and other styles
17

Liu, Junying, Guangdong Zhang, Yanping Lv, Xiaoyang Zhang, Cui Ying, Suocheng Yang, Xin Kong, and Yanzhang Yu. "SGK2 promotes hepatocellular carcinoma progression and mediates GSK-3β/β-catenin signaling in HCC cells." Tumor Biology 39, no. 6 (June 2017): 101042831770040. http://dx.doi.org/10.1177/1010428317700408.

Full text
APA, Harvard, Vancouver, ISO, and other styles
18

Liu, Yang, Junying liu, Xin Kong, Han Li, Jianying Shao, and Ziting Jiang. "SGK2 is overexpressed in colon cancer and promotes epithelial-mesenchymal transition in colon cancer cells." European Journal of Surgical Oncology 46, no. 10 (October 2020): 1912–17. http://dx.doi.org/10.1016/j.ejso.2020.06.002.

Full text
APA, Harvard, Vancouver, ISO, and other styles
19

Rodrigues, Gisele O. L., Wenqing Li, Sarah Cramer, Livia W. Campos, Priscila P. Zenatti, Angelo A. B. A. Laranjeira, Julie A. Hixon, et al. "Identification of Genetic Alterations Associated with Mutant IL7Ralpha in T-ALL." Blood 128, no. 22 (December 2, 2016): 5272. http://dx.doi.org/10.1182/blood.v128.22.5272.5272.

Full text
Abstract:
Abstract The IL7/IL7R mediated signaling is essential for normal development and homeostasis of T cell precursors. Early studies have shown that around 10% of patients with Acute lymphoblastic leukemia T cell (T-ALL) have mutations in the alpha chain of the receptor for IL7 (IL-7Ralpha) driving constitutive signaling via JAK1 and independent of IL-7, gamma-chain or JAK3. Some genetic changes are important factors to initiate leukemia, but in many cases these changes are insufficient to achieve the complete leukemic phenotype, suggesting that collaborative oncogenic mutations may be present. To identify candidate mutations that work in collaboration with the oncogenic IL7R, we performed exome sequencing and SNP-CNV-Array assay on a group of eight primary T-ALL samples carrying the IL7R mutation (T-ALL-IL7Rmut). The microarray was performed using Cytoscan HD - Affymetrix and CNVs were detected by ChAs software, version 2.0.1.2. For exome sequencing we used Illumina Hiseq2000 platform and Agilent SureSelect V4 51M Capture kit (mean sequencing depths of 80X / 50X for leukemia and remission samples, respectively). Somatic Single Nucleotide Variants (SNVs) and Small Insertion/Deletion (InDels) were detected using VarScan, and mutations were functionally annotated using ANNOVAR. All somatic mutations detected were manually curated. We found 17 genes recurrently mutated (in ≥ 2 cases) and chose five of them for further analyses due to their previous involvement in ALL (PHF6, RB1, CTCF, SGK223 and DNM2). Ongoing experiments are being conducted to determine whether these recurrent mutations can collaborate functionally with mutIL7R by co-transfection into immature murine thymocytes, transplanting into mice and determining incidence of leukemia. Disclosures No relevant conflicts of interest to declare.
APA, Harvard, Vancouver, ISO, and other styles
20

Wang, Haoxun, Da Xu, May Fern Toh, Alan C. Pao, and Guofeng You. "Serum- and glucocorticoid-inducible kinase SGK2 regulates human organic anion transporters 4 via ubiquitin ligase Nedd4-2." Biochemical Pharmacology 102 (February 2016): 120–29. http://dx.doi.org/10.1016/j.bcp.2015.11.024.

Full text
APA, Harvard, Vancouver, ISO, and other styles
21

Qin, Luye, Kaijie Ma, and Zhen Yan. "Chemogenetic Activation of Prefrontal Cortex in Shank3-Deficient Mice Ameliorates Social Deficits, NMDAR Hypofunction, and Sgk2 Downregulation." iScience 17 (July 2019): 24–35. http://dx.doi.org/10.1016/j.isci.2019.06.014.

Full text
APA, Harvard, Vancouver, ISO, and other styles
22

Pennington, Katie L., Colten M. McEwan, James Woods, Colin M. Muir, A. G. Pramoda Sahankumari, Riley Eastmond, Eranga R. Balasooriya, et al. "SGK2, 14-3-3, and HUWE1 Cooperate to Control the Localization, Stability, and Function of the Oncoprotein PTOV1." Molecular Cancer Research 20, no. 2 (October 15, 2021): 231–43. http://dx.doi.org/10.1158/1541-7786.mcr-20-1076.

Full text
APA, Harvard, Vancouver, ISO, and other styles
23

Baldwin, Amy, Dorre A. Grueneberg, Karin Hellner, Jacqueline Sawyer, Miranda Grace, Wenliang Li, Ed Harlow, and Karl Munger. "Kinase requirements in human cells: V. Synthetic lethal interactions between p53 and the protein kinases SGK2 and PAK3." Proceedings of the National Academy of Sciences 107, no. 28 (June 28, 2010): 12463–68. http://dx.doi.org/10.1073/pnas.1007462107.

Full text
APA, Harvard, Vancouver, ISO, and other styles
24

Friedrich, B., Y. Feng, P. Cohen, T. Risler, A. Vandewalle, S. Bröer, J. Wang, D. Pearce, and F. Lang. "The serine/threonine kinases SGK2 and SGK3 are potent stimulators of the epithelial Na+ channel α,β,γ-ENaC." Pflügers Archiv - European Journal of Physiology 445, no. 6 (January 21, 2003): 693–96. http://dx.doi.org/10.1007/s00424-002-0993-8.

Full text
APA, Harvard, Vancouver, ISO, and other styles
25

Jäger, Roland, Tiina Berg, Ashot Harutyunyan, Thorsten Klampfl, Francesco Passamonti, Elisa Rumi, Daniela Pietra, et al. "Characterization of Chromosome 20q Deletions In Myeloproliferative Neoplasms Using Microarray Karyotyping and Next-Generation Sequencing." Blood 116, no. 21 (November 19, 2010): 4099. http://dx.doi.org/10.1182/blood.v116.21.4099.4099.

Full text
Abstract:
Abstract Abstract 4099 Deletions on chromosome 20q (del20q) are among the most frequent cytogenetic aberrations in myeloid disorders. Mapping of common deleted regions (CDRs) has the potential to link often large deletions to single gene defects. In the past years 20q CDRs from several patient cohorts have been reported, most of them combining patients with different myeloid malignancies, such as myeloproliferative neoplasms (MPN), chronic myeloid leukemia and myelodysplastic syndrome. However, it is not clear whether the same genes within del20q are relevant for pathogenesis in the different myeloid diseases. We aimed to delineate a common deleted region exclusively based on a substantial number of MPN patients. Using a copy number assay, we screened for del20q in a total of 822 MPN patients combined from three independent MPN patient cohorts. Del20q was present in granulocyte DNA from 11 patients (1.1%). We consequently mapped the 11 deletions using Affymetrix 6.0 microarray karyotyping, resulting in a common deleted region of 6.4 Mb size, comprising 82 transcribed genes. In a next step, we aimed to investigate the remaining undeleted allele for the presence of somatic mutations. We applied a next generation sequencing approach and sequenced 774 coding exons within our del20q CDR in 11 patients with del20q. We prepared a DNA pool containing equal amounts of granulocyte DNA from each patient and amplified 774 exons in separate PCR reactions. The PCR reactions were pooled, concatemerized by ligation, refragmented, and prepared for a single-end 36bp sequencing read on a Genome Analyzer IIx (Illumina). The single-end read delivered a coverage between 1000- and 5000-fold per exonic base. We identified five putative variants in the genes SGK2, SEMG1, SEMG2, WFDC9 and SLC13A3 that were non-synonymous and were not annotated in any of the public SNP databases. Further validation in the single patients using classical capillary sequencing identified heterozygous calls in SGK2, SEMG1 and SEMG2 as false positives. The putative variants in WFDC9 (position chr20:43670771; G/A; NCBI36/hg18) and SLC13A3 (position chr20:44654462; C/G; NCBI36/hg18) could be confirmed in granulocyte DNA from a subset of the del20q patients. However, the variants could also be detected in DNA from a control non-myeloid tissue indicating their germ line origin. The variants were present in healthy individuals at variable frequencies, identifying them as novel SNPs presumably not involved in MPN pathogenesis. From the absence of mutations on the undeleted allele in patients with del20q we can conclude that haploinsufficiency is the most likely functional consequence of tumor suppressor inactivation within the del20q CDR in myeloproliferative neoplasms. Disclosures: No relevant conflicts of interest to declare.
APA, Harvard, Vancouver, ISO, and other styles
26

Park, In Ja, Yun Suk Yu, Bilal Mustafa, Jin Young Park, Yong Bae Seo, Gun-Do Kim, Jinpyo Kim, et al. "A Nine-Gene Signature for Predicting the Response to Preoperative Chemoradiotherapy in Patients with Locally Advanced Rectal Cancer." Cancers 12, no. 4 (March 26, 2020): 800. http://dx.doi.org/10.3390/cancers12040800.

Full text
Abstract:
Preoperative chemoradiotherapy (PCRT) and subsequent surgery is the standard multimodal treatment for locally advanced rectal cancer (LARC), albeit PCRT response varies among the individuals. This creates a dire necessity to identify a predictive model to forecast treatment response outcomes and identify patients who would benefit from PCRT. In this study, we performed a gene expression study using formalin-fixed paraffin-embedded (FFPE) tumor biopsy samples from 156 LARC patients (training cohort n = 60; validation cohort n = 96); we identified the nine-gene signature (FGFR3, GNA11, H3F3A, IL12A, IL1R1, IL2RB, NKD1, SGK2, and SPRY2) that distinctively differentiated responders from non-responders in the training cohort (accuracy = 86.9%, specificity = 84.8%, sensitivity = 81.5%) as well as in an independent validation cohort (accuracy = 81.0%, specificity = 79.4%, sensitivity = 82.3%). The signature was independent of all pathological and clinical features and was robust in predicting PCRT response. It is readily applicable to the clinical setting using FFPE samples and Food and Drug Administration (FDA) approved hardware and reagents. Predicting the response to PCRT may aid in tailored therapies for respective responders to PCRT and improve the oncologic outcomes for LARC patients.
APA, Harvard, Vancouver, ISO, and other styles
27

Wang, Hui-Ching, Meng-Chun Chou, Chun-Chieh Wu, Leong-Perng Chan, Sin-Hua Moi, Mei-Ren Pan, Ta-Chih Liu, and Cheng-Hong Yang. "Application of the Interaction between Tissue Immunohistochemistry Staining and Clinicopathological Factors for Evaluating the Risk of Oral Cancer Progression by Hierarchical Clustering Analysis: A Case-Control Study in a Taiwanese Population." Diagnostics 11, no. 6 (May 21, 2021): 925. http://dx.doi.org/10.3390/diagnostics11060925.

Full text
Abstract:
The aim of this single-center case-control study is to investigate the feasibility and accuracy of oral cancer protein risk stratification (OCPRS) to analyze the risk of cancer progression. All patients diagnosed with oral cancer in Taiwan, between 2012 and 2014, and who underwent surgical intervention were selected for the study. The tissue was further processed for immunohistochemistry (IHC) for 21 target proteins. Analyses were performed using the results of IHC staining, clinicopathological characteristics, and survival outcomes. Novel stratifications with a hierarchical clustering approach and combinations were applied using the Cox proportional hazard regression model. Of the 163 participants recruited, 102 patients were analyzed, and OCPRS successfully identified patients with different progression-free survival (PFS) profiles in high-risk (53 subjects) versus low-risk (49 subjects) groups (p = 0.012). OCPRS was composed of cytoplasmic PLK1, phosphoMet, and SGK2 IHC staining. After controlling for the influence of clinicopathological features, high-risk patients were 2.33 times more likely to experience cancer progression than low-risk patients (p = 0.020). In the multivariate model, patients with extranodal extension (HR = 2.66, p = 0.045) demonstrated a significantly increased risk for disease progression. Risk stratification with OCPRS provided distinct PFS groups for patients with oral cancer after surgical intervention. OCPRS appears suitable for routine clinical use for progression and prognosis estimation.
APA, Harvard, Vancouver, ISO, and other styles
28

Talarico, Cristina, Vincenzo Dattilo, Lucia D'Antona, Miranda Menniti, Cataldo Bianco, Francesco Ortuso, Stefano Alcaro, Silvia Schenone, Nicola Perrotti, and Rosario Amato. "SGK1, the New Player in the Game of Resistance: Chemo-Radio Molecular Target and Strategy for Inhibition." Cellular Physiology and Biochemistry 39, no. 5 (2016): 1863–76. http://dx.doi.org/10.1159/000447885.

Full text
Abstract:
The serum- and glucocorticoid-regulated kinase (SGK) family consists of three members, SGK1, SGK2 and SGK3, all displaying serine/threonine kinase activity and sharing structural and functional similarities with the AKT family of kinases. SGK1 was originally described as a key enzyme in the hormonal regulation of several ion channels and pumps. Over time, growing and impressive evidence has been accumulated, linking SGK1 to the cell survival, de-differentiation, cell cycle control, regulation of caspases, response to chemical, mechanical and oxidative injury in cancer models as well as to the control of mitotic stability. Much evidence shows that SGK1 is over-expressed in a variety of epithelial tumors. More recently, many contributions to the published literature demonstrate that SGK1 can mediate chemo-and radio-resistance during the treatment of various human tumors, both in vitro and in vivo. SGK1 appears therefore as a dirty player in the stress response to chemical and radio-agents, responsible of a selective advantage that favors the uncontrolled tumor progression and the selection of the most aggressive clones. The purpose of this review is the analysis of the literature describing SGK1 as central node of the cell resistance, and a summary of the possible strategies in the pharmacological targeting of SGK1.
APA, Harvard, Vancouver, ISO, and other styles
29

Ali, Raja Affendi Raja, Eden Ngah Den Low, and Norfilza M. Mokhtar. "Mo1130 SGK2 KNOCKDOWN BY GENE EDITING PROMOTES CELL PROLIFERATION BUT SUPPRESSES CELL MIGRATION AND INVASION IN IN-VITRO MODEL OF COLITIS-ASSOCIATED CANCER." Gastroenterology 158, no. 6 (May 2020): S—798. http://dx.doi.org/10.1016/s0016-5085(20)32671-8.

Full text
APA, Harvard, Vancouver, ISO, and other styles
30

Wang, Hui-Ching, Leong-Perng Chan, Chun-Chieh Wu, Hui-Hua Hsiao, Yi-Chang Liu, Shih-Feng Cho, Jeng-Shiun Du, et al. "Progression Risk Score Estimation Based on Immunostaining Data in Oral Cancer Using Unsupervised Hierarchical Clustering Analysis: A Retrospective Study in Taiwan." Journal of Personalized Medicine 11, no. 9 (September 13, 2021): 908. http://dx.doi.org/10.3390/jpm11090908.

Full text
Abstract:
This study aimed to investigate whether the progression risk score (PRS) developed from cytoplasmic immunohistochemistry (IHC) biomarkers is available and applicable for assessing risk and prognosis in oral cancer patients. Participants in this retrospective case-control study were diagnosed between 2012 and 2014 and subsequently underwent surgical intervention. The specimens from surgery were stained by IHC for 16 cytoplasmic target markers. We evaluated the results of IHC staining, clinical and pathological features, progression-free survival (PFS), and overall survival (OS) of 102 oral cancer patients using a novel estimation approach with unsupervised hierarchical clustering analysis. Patients were stratified into high-risk (52) and low-risk (50) groups, according to their PRS; a metric consisting of cytoplasmic PLK1, PhosphoMet, SGK2, and SHC1 expression. Moreover, PRS could be extended for use in the Cox proportional hazard regression model to estimate survival outcomes with associated clinical parameters. Our study findings revealed that the high-risk patients had a significantly increased risk in cancer progression compared with low-risk patients (hazard ratio (HR) = 2.20, 95% confidence interval (CI) = 1.10–2.42, p = 0.026). After considering the influences of demographics, risk behaviors, and tumor characteristics, risk estimation with PRS provided distinct PFS groups for patients with oral cancer (p = 0.017, p = 0.019, and p = 0.020). Our findings support that PRS could serve as an ideal biomarker for clinical use in risk stratification and progression assessment in oral cancer.
APA, Harvard, Vancouver, ISO, and other styles
31

Palmada, M., M. Dieter, A. Speil, C. Böhmer, A. F. Mack, H. J. Wagner, K. Klingel, et al. "Regulation of intestinal phosphate cotransporter NaPi IIb by ubiquitin ligase Nedd4–2 and by serum- and glucocorticoid-dependent kinase 1." American Journal of Physiology-Gastrointestinal and Liver Physiology 287, no. 1 (July 2004): G143—G150. http://dx.doi.org/10.1152/ajpgi.00121.2003.

Full text
Abstract:
Serum and glucocorticoid-inducible kinase 1 (SGK1) is highly expressed in enterocytes. The significance of the kinase in regulation of intestinal function has, however, remained elusive. In Xenopus laevis oocytes, SGK1 stimulates the epithelial Na+ channel by phosphorylating the ubiquitin ligase Nedd4–2, which regulates channels by ubiquitination leading to subsequent degradation of the channel protein. Thus the present study has been performed to explore whether SGK1 regulates transport systems expressed in intestinal epithelial cells, specifically type IIb sodium-phosphate (Na+-Pi) cotransporter (NaPi IIb). Immunohistochemistry in human small intestine revealed SGK1 colocalization with Nedd4–2 in villus enterocytes. For functional analysis cRNA encoding NaPi IIb, the SGK isoforms and/or the Nedd4–2 were injected into X. laevis oocytes, and transport activity was quantified as the substrate-induced current ( IP). Exposure to 3 mM phosphate induces an IP in NaPi IIb-expressing oocytes. Coinjection of Nedd4–2, but not the catalytically inactive mutant C938SNedd4–2, significantly downregulates IP, whereas the coinjection of S422DSGK1 markedly stimulates IP and even fully reverses the effect of Nedd4–2 on IP. The effect of S422DSGK1 on NaPi IIb is mimicked by wild-type SGK3 but not by wild-type SGK2, constitutively active T308D,S473DPKB, or inactive K127NSGK1. Moreover, S422DSGK1 and SGK3 phosphorylate Nedd4–2. In conclusion, SGK1 stimulates the NaPi IIb, at least in part, by phosphorylating and thereby inhibiting Nedd4–2 binding to its target. Thus the present study reveals a novel signaling pathway in the regulation of intestinal phosphate transport, which may be important for regulation of phosphate balance.
APA, Harvard, Vancouver, ISO, and other styles
32

Lang, Florian, Christoph Böhmer, Monica Palmada, Guiscard Seebohm, Nathalie Strutz-Seebohm, and Volker Vallon. "(Patho)physiological Significance of the Serum- and Glucocorticoid-Inducible Kinase Isoforms." Physiological Reviews 86, no. 4 (October 2006): 1151–78. http://dx.doi.org/10.1152/physrev.00050.2005.

Full text
Abstract:
The serum- and glucocorticoid-inducible kinase-1 (SGK1) is ubiquitously expressed and under genomic control by cell stress (including cell shrinkage) and hormones (including gluco- and mineralocorticoids). Similar to its isoforms SGK2 and SGK3, SGK1 is activated by insulin and growth factors via phosphatidylinositol 3-kinase and the 3-phosphoinositide-dependent kinase PDK1. SGKs activate ion channels (e.g., ENaC, TRPV5, ROMK, Kv1.3, KCNE1/KCNQ1, GluR1, GluR6), carriers (e.g., NHE3, GLUT1, SGLT1, EAAT1–5), and the Na+-K+-ATPase. They regulate the activity of enzymes (e.g., glycogen synthase kinase-3, ubiquitin ligase Nedd4–2, phosphomannose mutase-2) and transcription factors (e.g., forkhead transcription factor FKHRL1, β-catenin, nuclear factor κB). SGKs participate in the regulation of transport, hormone release, neuroexcitability, cell proliferation, and apoptosis. SGK1 contributes to Na+ retention and K+ elimination of the kidney, mineralocorticoid stimulation of salt appetite, glucocorticoid stimulation of intestinal Na+/H+ exchanger and nutrient transport, insulin-dependent salt sensitivity of blood pressure and salt sensitivity of peripheral glucose uptake, memory consolidation, and cardiac repolarization. A common (∼5% prevalence) SGK1 gene variant is associated with increased blood pressure and body weight. SGK1 may thus contribute to metabolic syndrome. SGK1 may further participate in tumor growth, neurodegeneration, fibrosing disease, and the sequelae of ischemia. SGK3 is required for adequate hair growth and maintenance of intestinal nutrient transport and influences locomotive behavior. In conclusion, the SGKs cover a wide variety of physiological functions and may play an active role in a multitude of pathophysiological conditions. There is little doubt that further targets will be identified that are modulated by the SGK isoforms and that further SGK-dependent in vivo physiological functions and pathophysiological conditions will be defined.
APA, Harvard, Vancouver, ISO, and other styles
33

Oshima, Koichi, Hossein Khiabanian, Ana Carolina da Silva Almeida, Gannie Tzoneva, Francesco Abate, Alberto Ambesi-Impiombato, Marta Sanchez-Martin, et al. "Mutational Landscape, Clonal Evolution Patterns and Role of RAS Mutations in Relapsed Acute Lymphoblastic Leukemia." Blood 128, no. 22 (December 2, 2016): 4068. http://dx.doi.org/10.1182/blood.v128.22.4068.4068.

Full text
Abstract:
Abstract Acute Lymphoblastic Leukemia (ALL) is the most common malignancy in children. Altogether 90% of pediatric ALL patients achieve a complete hematologic remission with current high dose combination chemotherapy and 80% of them remain leukemia free. However, the outcome for patients showing refractory disease or those whose leukemia relapses after an initial transient response remains disappointingly poor with cure rates of less than 40%. To investigate genetic drivers of relapse and resistance and explore the specific roles of clonal evolution in disease progression and relapse here we performed whole-exome sequence analysis of matched diagnosis, germline (remission) and relapse DNA samples in a panel of 55 pediatric ALL patients including 33 T-cell ALLs and 22 B-cell precursor ALLs. These analyses identified an average of 9 mutations present in diagnostic samples and 17 mutations in relapsed leukemia DNAs. Phylogenetic tree analysis for each of the 48 cases with optimal variant call parameters analyzing their clonal evolution dynamics during disease progression, combined with whole genome sequencing of targeted samples with low exonic mutation input, showed that branched evolution in which relapse clones contain some, but not all genetic lesions present in the major clone at diagnosis as the primary mechanism driving tumor progression and relapse present in 45/48 (94%) cases. In addition, and consistent with previous reports we identified the presence of chemotherapy associated mutations in NT5C2 (10/55), TP53 (3/55), CREBBP (4/55) and the NR3C1 glucocorticoid receptor gene (2/55). However, and most strikingly, 23/27 (85%) recurrently mutated genes in this series with mutations preferentially selected or retained at the time of relapse (mutation never lost in the relapse clone) were not implicated in relapse ALL before (HTR3A, MED12, USP9X, CACNA1H, ODZ3, AACS, SAMD4A, ANO5, PAPPA, NAALADL2, HIST3H2A, FZD7, TBX15, NEB, GREB1L, PLXNA4, SGK223, TSC1, PTPRG, FGF10, SYCP2, TRPM3 and EYS). A branched pattern of genetic evolution and the presence of recurrent mutations selected at relapse support that chemotherapy imposes a strong Darwinian genetic selection in leukemic cell populations. In this context it is worth noting that RAS-MAPK pathway activating mutations in NRAS, KRAS and PTPN11 were present in 24/55 (44%) cases in our series. Interestingly, some leukemias showed retention or emergence of RAS mutant clones at relapse, while in others, RAS mutant clones present at diagnosis were replaced by RAS wild type populations, supporting a role for both positive and negative selection evolutionary pressures in clonal evolution of RAS-mutant leukemia. Most notably, and in agreement with this hypothesis, inducible expression of mutant KRAS in human ALL lines demonstrate that oncogenic KRAS G12D induces methotrexate resistance, but also improves leukemia response to vincristine; a phenotype perfectly recapitulated in a isogenic ALL leukemia model generated from a conditional inducible Kras G12D knockin mice. Mechanistically, KRAS G12 expression induces MAPK dependent abrogation of methotrexate induced apoptosis. Moreover, Kras mutant tumors show enhanced G2/M cell cycle arrest and apoptosis upon spindle poisoning with vincristine, a phenotype linked with increased PLK phosphorylation and transcriptional down-regulation of mitotic genes. Finally clonal competition assays demonstrate that the differential response to methotrexate and vincristine in isogenic Kras wild type and Kras mutant ALL cells results in clonal dominance of Kras G12D populations in cultures treated with methotrexate, while Kras wild type cells are selected the context of vincristine treatment. In all these results show novel insight on the genetics and mechanisms of clonal selection, disease progression and relapse in ALL and demonstrate a previously unrecognized dual role of RAS mutations in chemotherapy response. Disclosures Loh: Abbvie: Research Funding; Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees.
APA, Harvard, Vancouver, ISO, and other styles
34

Alidoust Saharkhiz Lahiji, Mahsa, and Fatemeh Safari. "Potential therapeutic effects of hAMSCs secretome on Panc1 pancreatic cancer cells through downregulation of SgK269, E-cadherin, vimentin, and snail expression." Biologicals, February 2022. http://dx.doi.org/10.1016/j.biologicals.2022.02.001.

Full text
APA, Harvard, Vancouver, ISO, and other styles
35

Xu, Ci, Meichao Zhang, Lei Bian, Yanyan Li, Yuan Yao, and Dong Li. "N-glycosylated SGK196 suppresses the metastasis of basal-like breast cancer cells." Oncogenesis 9, no. 1 (January 2020). http://dx.doi.org/10.1038/s41389-019-0188-1.

Full text
Abstract:
AbstractSGK196 is a protein O-mannose kinase involved in an indispensable phosphorylation step during laminin-binding glycan synthesis on alpha-dystroglycan (α-DG). However, the function of SGK196 in cancer diseases remains elusive. In the current study, we demonstrated that SGK196 is primarily modified by N-glycosylation in breast cancer (BC) cells. Furthermore, gain and loss-of-function studies showed that N-glycosylated SGK196 suppresses cell migration, invasion, and metastasis in BC, particularly in the basal-like breast cancer (BLBC) type. In addition, we found that SGK196 N-glycosylation performs the regulatory function through the PI3K/AKT/GSK3β signaling pathway. Collectively, our results show that N-glycosylated SGK196 plays suppression roles in BLBC metastases, therefore providing new insights into SGK196 function in BC.
APA, Harvard, Vancouver, ISO, and other styles
36

Park, Chul-Hong, Jiyoung Moon, Minsung Park, Helia Cheng, Jisu Lee, and Ji Suk Chang. "Protein Kinase SGK2 Is Induced by the β3 Adrenergic Receptor-cAMP-PKA-PGC-1α/NT-PGC-1α Axis but Dispensable for Brown/Beige Adipose Tissue Thermogenesis." Frontiers in Physiology 12 (November 25, 2021). http://dx.doi.org/10.3389/fphys.2021.780312.

Full text
Abstract:
Brown and beige adipocytes are specialized to dissipate energy as heat. Sgk2, encoding a serine/threonine kinase, has been identified as a brown and beige adipocyte-specific gene in rodents and humans; however, its function in brown/beige adipocytes remains unraveled. Here, we examined the regulation and role of Sgk2 in brown/beige adipose tissue thermogenesis. We found that transcriptional coactivators PGC-1α and NT-PGC-1α activated by the β3 adrenergic receptor-cAMP-PKA pathway are recruited to the Sgk2 promoter, triggering Sgk2 transcription in response to cold. SGK2 elevation was closely associated with increased serine/threonine phosphorylation of proteins carrying the consensus RxRxxS/T phosphorylation site. However, despite cold-dependent activation of SGK2, mice lacking Sgk2 exhibited normal cold tolerance at 4°C. In addition, Sgk2+/+ and Sgk2−/− mice induced comparable increases in energy expenditure during pharmacological activation of brown and beige adipose tissue with a β3AR agonist. In vitro loss- and gain-of-function studies further demonstrated that Sgk2 ablation or activation does not alter thermogenic gene expression and mitochondrial respiration in brown adipocytes. Collectively, our results reveal a new signaling component SGK2, although dispensable for cold-induced thermogenesis that adds an additional layer of complexity to the β3AR signaling network in brown/beige adipose tissue.
APA, Harvard, Vancouver, ISO, and other styles
37

Patel, Onisha, Michael D. W. Griffin, Santosh Panjikar, Weiwen Dai, Xiuquan Ma, Howard Chan, Celine Zheng, et al. "Structure of SgK223 pseudokinase reveals novel mechanisms of homotypic and heterotypic association." Nature Communications 8, no. 1 (October 27, 2017). http://dx.doi.org/10.1038/s41467-017-01279-9.

Full text
APA, Harvard, Vancouver, ISO, and other styles
38

Tactacan, Carole M., Yu Wei Phua, Ling Liu, Luxi Zhang, Emily S. Humphrey, Mark Cowley, Mark Pinese, Andrew V. Biankin, and Roger J. Daly. "The pseudokinase SgK223 promotes invasion of pancreatic ductal epithelial cells through JAK1/Stat3 signaling." Molecular Cancer 14, no. 1 (July 29, 2015). http://dx.doi.org/10.1186/s12943-015-0412-3.

Full text
APA, Harvard, Vancouver, ISO, and other styles
39

Kurokawa, Suguru, Masato Yoneda, Yuji Ogawa, Yasushi Honda, Takaomi Kessoku, Kento Imajo, Satoru Saito, Atsushi Nakajima, and Kikuko Hotta. "Two differentially methylated region networks in nonalcoholic fatty liver disease, viral hepatitis, and hepatocellular carcinoma." BMC Gastroenterology 22, no. 1 (June 2, 2022). http://dx.doi.org/10.1186/s12876-022-02360-4.

Full text
Abstract:
Abstract Background We previously reported that two differentially methylated region (DMR) networks identified by DMR and co-methylation analyses are strongly correlated with the fibrosis stages of nonalcoholic fatty liver disease (NAFLD). In the current study, we examined these DMR networks in viral hepatitis and hepatocellular carcinoma (HCC). Methods We performed co-methylation analysis of DMRs using a normal dataset (GSE48325), two NAFLD datasets (JGAS000059 and GSE31803), and two HCC datasets (GSE89852 and GSE56588). The dataset GSE60753 was used for validation. Results One DMR network was clearly observed in viral hepatitis and two HCC populations. Methylation levels of genes in this network were higher in viral hepatitis and cirrhosis, and lower in HCC. Fatty acid binding protein 1 (FABP1), serum/glucocorticoid regulated kinase 2 (SGK2), and hepatocyte nuclear factor 4 α (HNF4A) were potential hub genes in this network. Increased methylation levels of the FABP1 gene may be correlated with reduced protection of hepatocytes from oxidative metabolites in NAFLD and viral hepatitis. The decreased methylation levels of SGK2 may facilitate the growth and proliferation of HCC cells. Decreased methylation levels of HNF4A in HCC may be associated with tumorigenesis. The other DMR network was observed in NAFLD, but not in viral hepatitis or HCC. This second network included genes involved in transcriptional regulation, cytoskeleton organization, and cellular proliferation, which are specifically related to fibrosis and/or tumorigenesis in NAFLD. Conclusions Our results suggest that one DMR network was associated with fibrosis and tumorigenesis in both NAFLD and viral hepatitis, while the other network was specifically associated with NAFLD progression. Furthermore, FABP1, SGK2, and HNF4A are potential candidate targets for the prevention and treatment of HCC.
APA, Harvard, Vancouver, ISO, and other styles
40

Zhu, Qinyu, David Venzke, Ameya S. Walimbe, Mary E. Anderson, Qiuyu Fu, Lisa N. Kinch, Wei Wang, et al. "Structure of protein O-mannose kinase reveals a unique active site architecture." eLife 5 (November 23, 2016). http://dx.doi.org/10.7554/elife.22238.

Full text
Abstract:
The ‘pseudokinase’ SgK196 is a protein O-mannose kinase (POMK) that catalyzes an essential phosphorylation step during biosynthesis of the laminin-binding glycan on α-dystroglycan. However, the catalytic mechanism underlying this activity remains elusive. Here we present the crystal structure of Danio rerio POMK in complex with Mg2+ ions, ADP, aluminum fluoride, and the GalNAc-β3-GlcNAc-β4-Man trisaccharide substrate, thereby providing a snapshot of the catalytic transition state of this unusual kinase. The active site of POMK is established by residues located in non-canonical positions and is stabilized by a disulfide bridge. GalNAc-β3-GlcNAc-β4-Man is recognized by a surface groove, and the GalNAc-β3-GlcNAc moiety mediates the majority of interactions with POMK. Expression of various POMK mutants in POMK knockout cells further validated the functional requirements of critical residues. Our results provide important insights into the ability of POMK to function specifically as a glycan kinase, and highlight the structural diversity of the human kinome.
APA, Harvard, Vancouver, ISO, and other styles
41

Wang, Wen-Chung, and Yen-Chein Lai. "DUSP5 and PHLDA1 mutations in mature cystic teratomas of the ovary identified on whole-exome sequencing may explain teratoma characteristics." Human Genomics 16, no. 1 (October 26, 2022). http://dx.doi.org/10.1186/s40246-022-00424-w.

Full text
Abstract:
Abstract Background Mature cystic teratomas of the ovary are the most common type of germ cell tumor, comprising 33% of ovarian tumors. Studying these tumors may result in a better understanding of their stepwise developmental processes and molecular bases and provide useful information for the development of tissue-engineering technologies. Methods In the present study, 9 mature cystic teratomas of the ovary were analyzed by whole-exome sequencing and the results were compared with the Catalogue of Somatic Mutations in Cancer and dbSNP databases. Results Mutations were validated in 15 genes with alterations in all 9 (100%) samples and changes in protein coding. The top 10 mutated genes were FLG, MUC17, MUC5B, RP1L1, NBPF1, GOLGA6L2, SLC29A3, SGK223, PTGFRN, and FAM186A. Moreover, 7 variants in exons with changes in protein coding are likely of importance in the development of mature cystic teratomas of the ovary, namely PTGFRN, DUSP5, MPP2, PHLDA1, PRR21, GOLGA6L2, and KRTAP4-2. Conclusions These genetic alterations may play an important etiological role in teratoma formation. Moreover, novel mutations in DUSP5 and PHLDA1 genes found on whole-exome sequencing may help to explain the characteristics of teratomas.
APA, Harvard, Vancouver, ISO, and other styles
42

Ranzuglia, Valentina, Maura Sonego, Alessandra Dall’Acqua, Ilenia Pellarin, Sara D’Andrea, Ilaria Lorenzon, Sara Lovisa, et al. "Inhibition of SGK2, a Novel Autophagy Modulator, Sensitizes Cancer Cells to Platinum Drugs." SSRN Electronic Journal, 2018. http://dx.doi.org/10.2139/ssrn.3238289.

Full text
APA, Harvard, Vancouver, ISO, and other styles
43

Schnackenberg, Christine G., Melissa H. Costell, Roberta E. Bernard, Kristine K. Minuti, Eugene T. Grygielko, Michael J. Parsons, Nicholas J. Laping, and Graham Duddy. "Compensatory role for Sgk2 mediated sodium reabsorption during salt deprivation in Sgk1 knockout mice." FASEB Journal 21, no. 5 (April 2007). http://dx.doi.org/10.1096/fasebj.21.5.a508-a.

Full text
APA, Harvard, Vancouver, ISO, and other styles
44

"Serum/glucocorticoid-regulated kinase 2 (SGK2); p21 protein (Cdc42 Rac)-activated kinase 3 (PAK3)." Science-Business eXchange 3, no. 28 (July 2010): 857. http://dx.doi.org/10.1038/scibx.2010.857.

Full text
APA, Harvard, Vancouver, ISO, and other styles
45

He, Peijian, Florian Lang, and Chris Yun. "The Differential Role of SGK3 from SGK1 and SGK2 in Activation of NHE3 by Glucocorticoid." FASEB Journal 25, S1 (April 2011). http://dx.doi.org/10.1096/fasebj.25.1_supplement.1038.4.

Full text
APA, Harvard, Vancouver, ISO, and other styles
46

Gotoh, Saki, and Masahiko Negishi. "Statin-activated nuclear receptor PXR promotes SGK2 dephosphorylation by scaffolding PP2C to induce hepatic gluconeogenesis." Scientific Reports 5, no. 1 (September 22, 2015). http://dx.doi.org/10.1038/srep14076.

Full text
APA, Harvard, Vancouver, ISO, and other styles
47

Kraja, Aldi T., Mary F. Feitosa, Daniel Chasman, Yun J. Sung, Thomas W. Winkler, Ioanna Ntalla, Hugues Aschard, et al. "Abstract P530: Pleiotropic Effects on Blood Pressure Traits Using Genome-wide Analysis of Gene-alcohol Interactions." Hypertension 70, suppl_1 (September 2017). http://dx.doi.org/10.1161/hyp.70.suppl_1.p530.

Full text
Abstract:
We tested for pleiotropy in European ancestry subjects (N>90K) via GWAS of systolic and diastolic blood pressure (BP), mean arterial pressure, and pulse pressure, using gene (G)-alcohol consumption (E) interactions. The approach was a correlated meta-analysis (PMCID-PMC3773990) that combined simultaneously the 4 BP traits genome-wide GxE interactions summary meta-P values. This approach adjusts for correlations among single traits at the genomic level. A variant was considered pleiotropic when the overall correlated meta-analysis yielded P ≤5E-08 and GxE meta- P ≤E-04 for at least two single traits. The novel pleiotropic variants localize in eight loci. TTLL7 (1p31.1) is a tubulin modifier. DYRK3 (1q32.1) is a transcription regulator. MAPKAPK2 (1q32.1) is a stress-activated serine/threonine-protein kinase involved in cytokine production especially for TNF , IL6 and phosphorylates (among others) LSP1 , identified in our GWAS GxE study for individual BP traits. FSTL5 (4q32.2) is annotated as calcium ion binding . A locus at 11q13.1 includes SNX32 , EFEMP2, and FOSL1 . FOSL1 variants may regulate expression of SNX32 . EFEMP2 is implicated in blood coagulation. CATSPER2 (15q15.3) is a cation channel. CCDC151 (19p13.2) is an outer dynein arm assembly. The functions of two other loci (17q22 and 18q22.3) are unknown. We also identified 4 pleiotropic loci ( SGK223 , TNKS , GATA4 , FTO ) that were found significant at our GxE meta-GWAS of single traits in 572K multi-ancestry individuals. In addition, we detected 24 pleiotropic BP-known loci. Some of these genes relate to alcohol consumption (e.g., BLK , GATA4 , FTO ). TNKS , MAPKAPK2 and FSTL5 interact with the Wnt/β-catenin signaling pathway, which contributes to hypertension. Several pleiotropic variants showed features of regulation by locating at promoter and enhancer histone marks, at DNAse, at proteins binding sites and being eQTL. The 36 novel and BP-known loci comprising 86 significant genes were enriched for Hypertension , Cardiac arrhythmias , Myocardial infarction , Atrial fibrillation, and Left ventricular hypertrophy . Our correlated meta-analysis of GxE interaction approach identified novel pleiotropic loci and validated known BP loci, thus providing insights into the mechanisms of hypertension.
APA, Harvard, Vancouver, ISO, and other styles
48

Safari, Fatemeh, Nasim Shafiee Nejad, and Azadeh Aghaei Nejad. "The inhibition of Panc1 cancer cells invasion by hAMSCs secretome through suppression of tyrosine phosphorylation of SGK223 (at Y411 site), c-Src (at Y416, Y530 sites), AKT activity, and JAK1/Stat3 signaling." Medical Oncology 39, no. 3 (January 20, 2022). http://dx.doi.org/10.1007/s12032-022-01649-4.

Full text
APA, Harvard, Vancouver, ISO, and other styles
49

Li, Changwei, Xueli Yang, Jiang He, James E. Hixson, Dongfeng Gu, Dabeeru C. Rao, Cashell E. Jaquish, et al. "Abstract MP15: Single And Joint Associations Of Genetic Variants In The Serum/glucocorticoid Regulated Kinase (sgk) Genes With Blood Pressure Responses To Sodium Intake: The Gensalt Study." Circulation 129, suppl_1 (March 25, 2014). http://dx.doi.org/10.1161/circ.129.suppl_1.mp15.

Full text
Abstract:
Background: Serum and glucocorticoid regulated kinase (SGK) plays a critical role in the regulation of renal sodium transport. We examined the association between SGK genes and salt sensitivity of blood pressure (BP) using single-marker and gene-based association analyses. Methods: A 7-day low-sodium (51.3 mmol sodium/day) followed by a 7-day high-sodium intervention (307.8 mmol sodium/day) was conducted among 1,906 Chinese participants. BP measurements were obtained at baseline and each intervention using a random-zero sphygmomanometer. Additive associations between each SNP and salt-sensitivity phenotypes were assessed using a mixed linear regression model to account for family dependencies. Gene-based analyses were conducted using the truncated p-value method. The Bonferroni-method was used to adjust for multiple testing in all analyses. Results: In single-marker association analyses, SGK1 marker rs2758151 was significantly associated with diastolic BP (DBP) response to high-sodium intervention (P=0.0010). DBP responses (95% confidence interval) to high-sodium intervention for genotypes C/C, C/T, and T/T were 2.04 (1.57 to 2.52), 1.79 (1.42 to 2.16), and 0.85 (0.30 to 1.41) mmHg, respectively. Similar non-significant trends were observed for SBP and MAP responses (P=0.15 and 0.0026, respectively). In addition, gene-based analyses demonstrated significant associations between SGK1 and SBP, DBP and MAP responses to high sodium intervention (P=0.0002, 0.0076, and 0.00001, respectively). Neither SGK2 nor SGK3 were associated with the salt-sensitivity phenotypes in single-maker and gene-based analyses. Conclusions: The current study identified single-marker and gene-based association of the SGK1 gene and BP salt-sensitivity in the Han Chinese population. Further studies are warranted to identify causal SGK1 gene variants.
APA, Harvard, Vancouver, ISO, and other styles
50

Zengin, Talip, and Tuğba Önal-Süzek. "Analysis of genomic and transcriptomic variations as prognostic signature for lung adenocarcinoma." BMC Bioinformatics 21, S14 (September 2020). http://dx.doi.org/10.1186/s12859-020-03691-3.

Full text
Abstract:
Abstract Background Lung cancer is the leading cause of the largest number of deaths worldwide and lung adenocarcinoma is the most common form of lung cancer. In order to understand the molecular basis of lung adenocarcinoma, integrative analysis have been performed by using genomics, transcriptomics, epigenomics, proteomics and clinical data. Besides, molecular prognostic signatures have been generated for lung adenocarcinoma by using gene expression levels in tumor samples. However, we need signatures including different types of molecular data, even cohort or patient-based biomarkers which are the candidates of molecular targeting. Results We built an R pipeline to carry out an integrated meta-analysis of the genomic alterations including single-nucleotide variations and the copy number variations, transcriptomics variations through RNA-seq and clinical data of patients with lung adenocarcinoma in The Cancer Genome Atlas project. We integrated significant genes including single-nucleotide variations or the copy number variations, differentially expressed genes and those in active subnetworks to construct a prognosis signature. Cox proportional hazards model with Lasso penalty and LOOCV was used to identify best gene signature among different gene categories. We determined a 12-gene signature (BCHE, CCNA1, CYP24A1, DEPTOR, MASP2, MGLL, MYO1A, PODXL2, RAPGEF3, SGK2, TNNI2, ZBTB16) for prognostic risk prediction based on overall survival time of the patients with lung adenocarcinoma. The patients in both training and test data were clustered into high-risk and low-risk groups by using risk scores of the patients calculated based on selected gene signature. The overall survival probability of these risk groups was highly significantly different for both training and test datasets. Conclusions This 12-gene signature could predict the prognostic risk of the patients with lung adenocarcinoma in TCGA and they are potential predictors for the survival-based risk clustering of the patients with lung adenocarcinoma. These genes can be used to cluster patients based on molecular nature and the best candidates of drugs for the patient clusters can be proposed. These genes also have a high potential for targeted cancer therapy of patients with lung adenocarcinoma.
APA, Harvard, Vancouver, ISO, and other styles
We offer discounts on all premium plans for authors whose works are included in thematic literature selections. Contact us to get a unique promo code!

To the bibliography