Journal articles: 'Mediated pathways'

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ZHU, LING, TIMON CHENG-YI LIU, MIN WU, JIAN-QIN YUAN, and TONG-SHENG CHEN. "EXTRAOCULAR CELLULAR PHOTOTRANSDUCTION." Journal of Innovative Optical Health Sciences 02, no. 01 (January 2009): 93–100. http://dx.doi.org/10.1142/s1793545809000358.

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Photobiomodulation (PBM) is a modulation of monochromatic light or laser irradiation (LI) on biosystems. It is reviewed from the viewpoint of extraocular phototransduction in this paper. It was found that LI can induce extraocular phototransduction, and there may be an exact correspondence relationship of LI at different wavelengths and in different dose zones, and cellular signal transduction pathways. The signal transduction pathways can be classified into two types so that the Gs protein-mediated pathways belong to pathway 1, and the other pathways such as protein kinase Cs -mediated pathways and mitogen-activated protein kinase-mediated pathways belong to pathway 2. Almost all the present pathways found to mediate PBM belong to pathway 2, but there should be a pathway 1-mediated PBM. The previous studies were rather preliminary, and therefore further work should be done.

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Gorvin, Caroline M. "Insights into calcium-sensing receptor trafficking and biased signalling by studies of calcium homeostasis." Journal of Molecular Endocrinology 61, no. 1 (July 2018): R1—R12. http://dx.doi.org/10.1530/jme-18-0049.

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The calcium-sensing receptor (CASR) is a class C G-protein-coupled receptor (GPCR) that detects extracellular calcium concentrations, and modulates parathyroid hormone secretion and urinary calcium excretion to maintain calcium homeostasis. The CASR utilises multiple heterotrimeric G-proteins to mediate signalling effects including activation of intracellular calcium release; mitogen-activated protein kinase (MAPK) pathways; membrane ruffling; and inhibition of cAMP production. By studying germline mutations in the CASR and proteins within its signalling pathway that cause hyper- and hypocalcaemic disorders, novel mechanisms governing GPCR signalling and trafficking have been elucidated. This review focusses on two recently described pathways that provide novel insights into CASR signalling and trafficking mechanisms. The first, identified by studying a CASR gain-of-function mutation that causes autosomal dominant hypocalcaemia (ADH), demonstrated a structural motif located between the third transmembrane domain and the second extracellular loop of the CASR that mediates biased signalling by activating a novel β-arrestin-mediated G-protein-independent pathway. The second, in which the mechanism by which adaptor protein-2 σ-subunit (AP2σ) mutations cause familial hypocalciuric hypercalcaemia (FHH) was investigated, demonstrated that AP2σ mutations impair CASR internalisation and reduce multiple CASR-mediated signalling pathways. Furthermore, these studies showed that the CASR can signal from the cell surface using multiple G-protein pathways, whilst sustained signalling is mediated only by the Gq/11 pathway. Thus, studies of FHH- and ADH-associated mutations have revealed novel steps by which CASR mediates signalling and compartmental bias, and these pathways could provide new targets for therapies for patients with calcaemic disorders.

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Xu, Wen, Bei Wang, Yisong Gao, Yuxuan Cai, Jiali Zhang, Zhiyin Wu, Jiameng Wei, Chong Guo, and Chengfu Yuan. "Alkaloids Exhibit a Meaningful Function as Anticancer Agents by Restraining Cellular Signaling Pathways." Mini-Reviews in Medicinal Chemistry 22, no. 7 (April 2022): 968–83. http://dx.doi.org/10.2174/1389557521666211007114935.

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Abstract: Alkaloids are nitrogen-containing organic compounds widely found in natural products, which play an essential role in clinical treatment. Cellular signaling pathways in tumors are a series of enzymatic reaction pathways that convert extracellular signals into intracellular signals to produce biological effects. The ordered function of cell signaling pathways is essential for tumor cell proliferation, differentiation, and programmed death. This review describes the antitumor progression mediated by various alkaloids after inhibiting classical signaling pathways; related studies are systematically retrieved and collected through PubMed. We selected the four currently most popular pathways for discussion and introduced the molecular mechanisms mediated by alkaloids in different signaling pathways, including the NF-kB signaling pathway, PI3K/AKT signaling pathway, MAPK signaling pathway, and P53 signaling pathway. The research progress of alkaloids related to tumor signal transduction pathwa

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Kamarajan, Pachiyappan, Julius Bunek, Yong Lin, Gabriel Nunez, and Yvonne L. Kapila. "Receptor-interacting Protein Shuttles between Cell Death and Survival Signaling Pathways." Molecular Biology of the Cell 21, no. 3 (February 2010): 481–88. http://dx.doi.org/10.1091/mbc.e09-06-0530.

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Cross-talk between apoptosis and survival signaling pathways is crucial for regulating tissue processes and mitigating disease. We report that anoikis—apoptosis triggered by loss of extracellular matrix contacts—activates a CD95/Fas-mediated signaling pathway regulated by receptor-interacting protein (RIP), a kinase that shuttles between CD95/Fas-mediated cell death and integrin/focal adhesion kinase (FAK)-mediated survival pathways. RIP's death domain was critical for RIP and Fas association to mediate anoikis. Fas or RIP attenuation reduced this association and suppressed anoikis, whereas their overexpression had the reverse effect. Overexpressing FAK restored RIP and FAK association and inhibited anoikis. Thus, RIP shuttles between CD95/Fas death and FAK survival signaling to mediate anoikis.

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Wang, Wen-Horng, Gérald Grégori, Ronald L. Hullinger, and Ourania M. Andrisani. "Sustained Activation of p38 Mitogen-Activated Protein Kinase and c-Jun N-Terminal Kinase Pathways by Hepatitis B Virus X Protein Mediates Apoptosis via Induction of Fas/FasL and Tumor Necrosis Factor (TNF) Receptor 1/TNF-α Expression." Molecular and Cellular Biology 24, no. 23 (December 1, 2004): 10352–65. http://dx.doi.org/10.1128/mcb.24.23.10352-10365.2004.

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ABSTRACT Activation of the cellular stress pathways (c-Jun N-terminal kinase [JNK] and p38 mitogen-activated protein [MAP] kinase) is linked to apoptosis. However, whether both pathways are required for apoptosis remains unresolved. Hepatitis B virus X protein (pX) activates p38 MAP kinase and JNK pathways and, in response to weak apoptotic signals, sensitizes hepatocytes to apoptosis. Employing hepatocyte cell lines expressing pX, which was regulated by tetracycline, we investigated the mechanism of apoptosis by p38 MAP kinase and JNK pathway activation. Inhibition of the p38 MAP kinase pathway rescues by 80% the initiation of pX-mediated apoptosis, whereas subsequent apoptotic events involve both pathways. pX-mediated activation of p38 MAP kinase and JNK pathways is sustained, inducing the transcription of the death receptor family genes encoding Fas/FasL and tumor necrosis factor receptor 1 (TNFR1)/TNF-α and the p53-regulated Bax and Noxa genes. The pX-dependent expression of Fas/FasL and TNFR1/TNF-α mediates caspase 8 activation, resulting in Bid cleavage. In turn, activated Bid, acting with pX-induced Bax and Noxa, mediates the mitochondrial release of cytochrome c, resulting in the activation of caspase 9 and apoptosis. Combined antibody neutralization of FasL and TNF-α reduces by 70% the initiation of pX-mediated apoptosis. These results support the importance of the pX-dependent activation of both the p38 MAP kinase and JNK pathways in pX-mediated apoptosis and suggest that this mechanism of apoptosis occurs in vivo in response to weak apoptotic signals.

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Andriichuk, T. R., N. G. Raksha, and L. I. Ostapchenko. "RADIATION-MEDIATED SIGNALING PATHWAYS." Biological Markers in Fundamental and Clinical Medicine (collection of abstracts) 2, no. 1 (March 24, 2018): 77–78. http://dx.doi.org/10.29256/v.02.01.2018.escbm34.

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LIU, TIMON CHENG-YI, LING ZHU, and XIANG-BO YANG. "PHOTOBIOMODULATION-MEDIATED PATHWAY DIAGNOSTICS." Journal of Innovative Optical Health Sciences 06, no. 01 (January 2013): 1330001. http://dx.doi.org/10.1142/s1793545813300012.

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Cellular pathways are ordinarily diagnosed with pathway inhibitors, related gene regulation, or fluorescent protein markers. They are also suggested to be diagnosed with pathway activation modulation of photobiomodulation (PBM) in this paper. A PBM on a biosystem function depends on whether the biosystem is in its function-specific homeostasis (FSH). An FSH, a negative feedback response for the function to be performed perfectly, is maintained by its FSH-essential subfunctions and its FSH-non-essential subfunctions (FNSs). A function in its FSH or far from its FSH is called a normal or dysfunctional function. A direct PBM may self-adaptatively modulate a dysfunctional function until it is normal so that it can be used to discover the optimum pathways for an FSH to be established. An indirect PBM may self-adaptatively modulate a dysfunctional FNS of a normal function until the FNS is normal, and the normal function is then upgraded so that it can be used to discover the redundant pathways for a normal function to be upgraded.

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Tang, Xiao, Daqiao Guo, Changpo Lin, Zhenyu Shi, Ruizhe Qian, Weiguo Fu, Jianjun Liu, Xu Li, and Longhua Fan. "hCLOCK Causes Rho-Kinase-Mediated Endothelial Dysfunction and NF-κB-Mediated Inflammatory Responses." Oxidative Medicine and Cellular Longevity 2015 (2015): 1–9. http://dx.doi.org/10.1155/2015/671839.

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Background. The human Circadian Locomotor Output Cycle protein Kaput (CLOCK) gene was originally discovered as a regulator of essential human daily rhythms. This seemingly innocuous gene was then found to be associated with a multitude of human malignancies, via several biochemical pathways. We aimed to further investigate the role of hCLOCK in the hypoxia-oxidative stress response system at the biochemical level.Methods. Expression levels of Rho GTPases were measured in normoxic and hypoxic states. The effect of hCLOCK on the hypoxic response was evaluated with the use of a retroviral shRNA vector system, a Rho inhibitor, and a ROS scavenger by analyzing expression levels of hCLOCK, Rho GTPases, and NF-κB pathway effectors. Finally, in vitro ROS production and tube formation in HUVECs were assessed.Results. Hypoxia induces ROS production via hCLOCK. hCLOCK activates the RhoA and NF-κB signaling pathways. Conversely, inhibition of hCLOCK deactivates these pathways. Furthermore, inhibition of RhoA or decreased levels of ROS attenuate these pathways, but inhibition of RhoA does not lead to decreased levels of ROS. Overall findings show that hypoxia increases the expression of hCLOCK, which leads to ROS production, which then activates the RhoA and NF-κB pathways.Conclusion. Our findings suggest that hypoxic states induce vascular oxidative damage and inflammation via hCLOCK-mediated production of ROS, with subsequent activation of the RhoA and NF-κB pathways.

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Dusaban, Stephanie S., and Joan Heller Brown. "PLCε mediated sustained signaling pathways." Advances in Biological Regulation 57 (January 2015): 17–23. http://dx.doi.org/10.1016/j.jbior.2014.09.014.

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Zhang, Qing, Jia Liu, Mengmeng Zhang, Shujun Wei, Ruolan Li, Yongxiang Gao, Wei Peng, and Chunjie Wu. "Apoptosis Induction of Fibroblast-Like Synoviocytes Is an Important Molecular-Mechanism for Herbal Medicine along with its Active Components in Treating Rheumatoid Arthritis." Biomolecules 9, no. 12 (November 28, 2019): 795. http://dx.doi.org/10.3390/biom9120795.

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Rheumatoid arthritis (RA) is a known chronic autoimmune disease can cause joint deformity and even loss of joint function. Fibroblast-like synoviocytes (FLS), one of the main cell types in synovial tissues of RA patients, are key effector cells in the development of RA and are considered as promising therapeutic targets for treating RA. Herbal medicines are precious resources for finding novel agents for treating various diseases including RA. It is reported that induction of apoptosis in FLS is an important mechanism for the herbal medicines to treat RA. Consequently, this paper reviewed the current available references on pro-apoptotic effects of herbal medicines on FLS and summarized the related possible signal pathways. Taken together, the main related signal pathways are concluded as death receptors mediated apoptotic pathway, mitochondrial dependent apoptotic pathway, NF-κB mediated apoptotic pathways, mitogen-activated protein kinase (MAPK) mediated apoptotic pathway, endoplasmic reticulum stress (ERS) mediated apoptotic pathway, PI3K-Akt mediated apoptotic pathway, and other reported pathways such as janus kinase/signal transducers and activators of transcription (JAK-STAT) signal pathway. Understanding the apoptosis induction pathways in FLS of these herbal medicines will not only help clear molecular mechanisms of herbal medicines for treating RA but also be beneficial for finding novel candidate therapeutic drugs from natural herbal medicines. Thus, we expect the present review will highlight the importance of herbal medicines and its components for treating RA via induction of apoptosis in FLS, and provide some directions for the future development of these mentioned herbal medicines as anti-RA drugs in clinical.

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Zimmermann, Marcel, and Andreas S. Reichert. "How to get rid of mitochondria: crosstalk and regulation of multiple mitophagy pathways." Biological Chemistry 399, no. 1 (December 20, 2017): 29–45. http://dx.doi.org/10.1515/hsz-2017-0206.

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AbstractMitochondria are indispensable cellular organelles providing ATP and numerous other essential metabolites to ensure cell survival. Reactive oxygen species (ROS), which are formed as side reactions during oxidative phosphorylation or by external agents, induce molecular damage in mitochondrial proteins, lipids/membranes and DNA. To cope with this and other sorts of organellar stress, a multi-level quality control system exists to maintain cellular homeostasis. One critical level of mitochondrial quality control is the removal of damaged mitochondria by mitophagy. This process utilizes parts of the general autophagy machinery, e.g. for the formation of autophagosomes but also employs mitophagy-specific factors. Depending on the proteins utilized mitophagy is divided into receptor-mediated and ubiquitin-mediated mitophagy. So far, at least seven receptor proteins are known to be required for mitophagy under different experimental conditions. In contrast to receptor-mediated pathways, the Pink-Parkin-dependent pathway is currently the best characterized ubiquitin-mediated pathway. Recently two additional ubiquitin-mediated pathways with distinctive similarities and differences were unraveled. We will summarize the current state of knowledge about these multiple pathways, explain their mechanism, and describe the regulation and crosstalk between these pathways. Finally, we will review recent evidence for the evolutionary conservation of ubiquitin-mediated mitophagy pathways.

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Maquat, Lynne E., and Chenguang Gong. "Gene expression networks: competing mRNA decay pathways in mammalian cells." Biochemical Society Transactions 37, no. 6 (November 19, 2009): 1287–92. http://dx.doi.org/10.1042/bst0371287.

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Nonsense-mediated mRNA decay and Staufen1-mediated mRNA decay are mechanistically related pathways that serve distinct purposes. In the present article, we give an overview of each pathway. We describe how a factor that is common to both pathways results in their competition. We also explain how competition between the two pathways contributes to the differentiation of C2C12 myoblasts to multinucleated myotubes.

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Akçay, Nimet İlke, Rza Bashirov, and Şükrü Tüzmen. "Validation of signalling pathways: Case study of the p16-mediated pathway." Journal of Bioinformatics and Computational Biology 13, no. 02 (April 2015): 1550007. http://dx.doi.org/10.1142/s0219720015500079.

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p16 is recognized as a tumor suppressor gene due to the prevalence of its genetic inactivation in all types of human cancers. Additionally, p16 gene plays a critical role in controlling aging, regulating cellular senescence, detection and maintenance of DNA damage. The molecular mechanism behind these events involves p16-mediated signaling pathway (or p16- Rb pathway), the focus of our study. Understanding functional dependence between dynamic behavior of biological components involved in the p16-mediated pathway and aforesaid molecular-level events might suggest possible implications in the diagnosis, prognosis and treatment of human cancer. In the present work, we employ reverse-engineering approach to construct the most detailed computational model of p16-mediated pathway in higher eukaryotes. We implement experimental data from the literature to validate the model, and under various assumptions predict the dynamic behavior of p16 and other biological components by interpreting the simulation results. The quantitative model of p16-mediated pathway is created in a systematic manner in terms of Petri net technologies.

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Wang, Si Jia. "Role of Ubiquitin in the Survival of Legionella pneumophila in Eukaryotic Host Cells." McGill Science Undergraduate Research Journal 12, no. 1 (April 9, 2017): 44–49. http://dx.doi.org/10.26443/msurj.v12i1.44.

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Background: Eukaryotic cells use essential ubiquitin-mediated pathways in their defense against pathogenic bacteria, such as Legionella pneumophila, the intracellular pathogen of Legionnaire’s disease. Despite the protective role of these pathways, L. pneumophila virulence has evolved to secrete numerous effector proteins involved in co-opting host ubiquitin-mediated processes to facilitate their survival. Many of these effector proteins are of great research interest in the quest to demystify the molecular mechanisms underlying L. pneumophila pathogenesis as the bacterium has a vast repertoire of effector proteins. Methods: Articles were obtained from scientific literature databases such as PubMed and the McGill library. Selected articles provided an overview of the ubiquitination pathway, eukaryotic autophagy, L. pneumophila pathogenesis, and structural and functional analysis of L. pneumophila and other bacterial effectors involved in subverting host ubiquitin systems. Summary: This review discusses the current structural and functional characterization of L. pneumophila protein effectors involved in exploiting host ubiquitin machinery to facilitate intracellular bacterial survival. These protein effectors include those with E3 ubiquitin ligase activity, LubX, AnkB, and SidC, which respectively mediate bacterial nutrient acquisition, temporal regulation of other effectors, and remodelling of the L. pneumophila replicative niche; the SidE family of effectors, which mediates the first novel, single-enzyme ubiquitination pathway and deubiquitination; and ravZ, a protease promoting evasion of host autophagy. However, the exact molecular functions and biological consequences of these effectors as well as the full repertoire of L. pneumophila effectors facilitating ubiquitin-mediated survival still require further investigation.

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Sherer, Laura A., Mark E. Zweifel, and Naomi Courtemanche. "Dissection of two parallel pathways for formin-mediated actin filament elongation." Journal of Biological Chemistry 293, no. 46 (September 28, 2018): 17917–28. http://dx.doi.org/10.1074/jbc.ra118.004845.

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Formins direct the elongation of unbranched actin filaments that are incorporated into a diverse set of cytoskeletal structures. Elongation of formin-bound filaments occurs along two parallel pathways. The formin homology 2 (FH2) pathway allows actin monomers to bind directly to barbed ends bound by dimeric FH2 domains. The formin homology 1 (FH1) pathway involves transfer of profilin-bound actin to the barbed end from polyproline tracts located in the disordered FH1 domains. Here, we used a total internal reflection fluorescence (TIRF) microscopy-based fluorescence approach to determine the fraction of actin subunits incorporated via the FH1 and FH2 pathways during filament elongation mediated by two formins. We found that the fraction of filament elongation that occurs via each pathway directly depends on the efficiency of the other pathway, indicating that these two pathways compete with each other for subunit addition by formins. We conclude that this competition allows formins to compensate for changes in the efficiency of one pathway by adjusting the frequency of subunit addition via the other, thus increasing the overall robustness of formin-mediated actin polymerization.

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Grümmer, R., S. W. Hewitt, O. Traub, K. S. Korach, and E. Winterhager. "Different Regulatory Pathways of Endometrial Connexin Expression: Preimplantation Hormonal-Mediated Pathway Versus Embryo Implantation-Initiated Pathway1." Biology of Reproduction 71, no. 1 (July 1, 2004): 273–81. http://dx.doi.org/10.1095/biolreprod.103.024067.

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Li, Erguang, Dwayne Stupack, Richard Klemke, David A. Cheresh, and Glen R. Nemerow. "Adenovirus Endocytosis via αvIntegrins Requires Phosphoinositide-3-OH Kinase." Journal of Virology 72, no. 3 (March 1, 1998): 2055–61. http://dx.doi.org/10.1128/jvi.72.3.2055-2061.1998.

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ABSTRACT Integrins mediate cell adhesion and motility on the extracellular matrix, yet they also promote viral attachment and/or entry. Evidence is presented that adenovirus internalization by αvintegrins requires activation of phosphoinositide-3-OH kinase (PI3K), whereas αv integrin-mediated cell motility depends on the ERK1/ERK2 mitogen-activated protein kinase pathway. Interaction of adenovirus with αv integrins induced activation of PI3K. Pharmacologic or genetic disruption of endogenous PI3K activity blocked adenovirus internalization and virus-mediated gene delivery yet had no effect on integrin-mediated cell adhesion or motility. Therefore, integrin ligation engages distinct signaling pathways that promote viral endocytosis or cell movement.

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Rechsteiner, Martin. "Ubiquitin-Mediated Pathways for Intracellular Proteolysis." Annual Review of Cell Biology 3, no. 1 (November 1987): 1–30. http://dx.doi.org/10.1146/annurev.cb.03.110187.000245.

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CLARK, WILLIAM R., CRAIG M. WALSH, ALISON A. GLASS, FUMITAKA HAYASHI, MEHRDAD MATLOUBIAN, and RAFI AHMED. "Molecular Pathways of CTL-mediated Cytotoxicity." Immunological Reviews 146, no. 1 (August 1995): 33–44. http://dx.doi.org/10.1111/j.1600-065x.1995.tb00682.x.

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da Silva Correia, J., Y. Miranda, N. Leonard, J. Hsu, and R. J. Ulevitch. "Regulation of Nod1-mediated signaling pathways." Cell Death & Differentiation 14, no. 4 (December 22, 2006): 830–39. http://dx.doi.org/10.1038/sj.cdd.4402070.

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Matzke, Marjori A., and James A. Birchler. "RNAi-mediated pathways in the nucleus." Nature Reviews Genetics 6, no. 1 (January 2005): 24–35. http://dx.doi.org/10.1038/nrg1500.

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Fujiu, Katsuhito, and Ryozo Nagai. "Fibroblast-mediated pathways in cardiac hypertrophy." Journal of Molecular and Cellular Cardiology 70 (May 2014): 64–73. http://dx.doi.org/10.1016/j.yjmcc.2014.01.013.

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Dias, Andre, Emiliana Franco, and Vincent M. Figueredo. "Catecholamine-Mediated Pathways in Takotsubo Syndrome." JACC: Heart Failure 6, no. 8 (August 2018): 720–21. http://dx.doi.org/10.1016/j.jchf.2018.04.016.

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Saito, Yuji, and Bradford C. Berk. "Angiotensin II-mediated signal transduction pathways." Current Hypertension Reports 4, no. 2 (March 2002): 167–71. http://dx.doi.org/10.1007/s11906-002-0042-1.

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Kehry, M. R. "CD40-mediated signaling in B cells. Balancing cell survival, growth, and death." Journal of Immunology 156, no. 7 (April 1, 1996): 2345–48. http://dx.doi.org/10.4049/jimmunol.156.7.2345.

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Abstract Multimerization of CD40 molecules on B cells by binding CD40 ligand on activated T cells initiates signaling events essential for B cell differentiation. In mature B cells, CD40 mediates stimulation and costimulation of cell growth, switch recombination, and transcriptional regulation. CD40-mediated signaling also regulates cell death, rescuing B cells from anti-Ig-induced apoptosis and inducing the expression of the Fas surface molecule. Recent efforts to elucidate the biochemistry of CD40-mediated signaling pathways have identified members of the TRAF protein family that are associated with the cytoplasmic tail of CD40. CD40 cross-linking probably multimerizes TRAF proteins which may act as direct transcriptional regulators. Modulation of protein tyrosine kinase and protein tyrosine phosphatase activity also occurs after CD40-mediated signaling; however, a connection to the TRAF pathway has not been established. Multiple pathways of B cell triggering are probably integrated at the level of transcriptional activation to produce differentiation stage-specific B cell responses.

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Chiu, V. K., C. M. Walsh, C. C. Liu, J. C. Reed, and W. R. Clark. "Bcl-2 blocks degranulation but not fas-based cell-mediated cytotoxicity." Journal of Immunology 154, no. 5 (March 1, 1995): 2023–32. http://dx.doi.org/10.4049/jimmunol.154.5.2023.

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Abstract The ability of bcl-2 in target cells to block cell-mediated cytotoxicity by allospecific CTL was tested. The blocking effect was variable. Because killing by CTL involves two different pathways, degranulation (perforin plus granzymes) and fas, we examined the effect of bcl-2 on these pathways independently. Bcl-2 in target cells blocked apoptotic cell death induced either by cytotoxic granule extracts or by CTL killing under conditions in which the fas pathway is blocked. On the other hand, bcl-2 had no effect on target cell-killing either by Fas-specific mAb or by CTL capable of killing only via the fas pathway. These data suggest bcl-2 may block apoptotic lysis induced by perforin plus granzymes, but not apoptotic lysis induced via the fas pathway. Thus, any analysis of the effect of bcl-2 on apoptotic cell death in target cells killed by CTL must take into account the relative contributions of the degranulation vs fas pathways.

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Lloyd, James P. B. "The evolution and diversity of the nonsense-mediated mRNA decay pathway." F1000Research 7 (August 15, 2018): 1299. http://dx.doi.org/10.12688/f1000research.15872.1.

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Nonsense-mediated mRNA decay is a eukaryotic pathway that degrades transcripts with premature termination codons (PTCs). In most eukaryotes, thousands of transcripts are degraded by NMD, including many important regulators of development and stress response pathways. Transcripts can be targeted to NMD by the presence of an upstream ORF or by introduction of a PTC through alternative splicing. Many factors involved in the recognition of PTCs and the destruction of NMD targets have been characterized. While some are highly conserved, others have been repeatedly lost in eukaryotic lineages. Here, I outline the factors involved in NMD, our current understanding of their interactions and how they have evolved. I outline a classification system to describe NMD pathways based on the presence/absence of key NMD factors. These types of NMD pathways exist in multiple different lineages, indicating the plasticity of the NMD pathway through recurrent losses of NMD factors during eukaryotic evolution. By classifying the NMD pathways in this way, gaps in our understanding are revealed, even within well studied organisms. Finally, I discuss the likely driving force behind the origins of the NMD pathway before the appearance of the last eukaryotic common ancestor: transposable element expansion and the consequential origin of introns.

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Lloyd, James P. B. "The evolution and diversity of the nonsense-mediated mRNA decay pathway." F1000Research 7 (November 22, 2018): 1299. http://dx.doi.org/10.12688/f1000research.15872.2.

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Nonsense-mediated mRNA decay is a eukaryotic pathway that degrades transcripts with premature termination codons (PTCs). In most eukaryotes, thousands of transcripts are degraded by NMD, including many important regulators of developmental and stress response pathways. Transcripts can be targeted to NMD by the presence of an upstream ORF or by introduction of a PTC through alternative splicing. Many factors involved in the recognition of PTCs and the destruction of NMD targets have been characterized. While some are highly conserved, others have been repeatedly lost in eukaryotic lineages. Here, I detail the factors involved in NMD, our current understanding of their interactions and how they have evolved. I outline a classification system to describe NMD pathways based on the presence/absence of key NMD factors. These types of NMD pathways exist in multiple different lineages, indicating the plasticity of the NMD pathway through recurrent losses of NMD factors during eukaryotic evolution. By classifying the NMD pathways in this way, gaps in our understanding are revealed, even within well studied organisms. Finally, I discuss the likely driving force behind the origins of the NMD pathway before the appearance of the last eukaryotic common ancestor: transposable element expansion and the consequential origin of introns.

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Sethu, Swaminathan, and Alirio J. Melendez. "New developments on the TNFα-mediated signalling pathways." Bioscience Reports 31, no. 1 (October 21, 2010): 63–76. http://dx.doi.org/10.1042/bsr20100040.

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TNFα (tumour necrosis factor α) is an extensively studied pleiotropic cytokine associated with the pathogenesis of a variety of inflammatory diseases. It elicits a wide spectrum of cellular responses which mediates and regulates inflammation, immune response, cell survival, proliferation and apoptosis. TNFα initiates its responses by binding to its receptors. TNFα-induced effector responses are mediated by the actions and interactions among the various intracellular signalling mediators in the cell. TNFα induces both survival and apoptotic signal in a TRADD (TNF receptor-associated DD)-dependent and -independent way. The signals are further transduced via a variety of signalling mediators, including caspases, MAPKs (mitogen-activated protein kinases), phospholipid mediators and miRNA/miR (microRNA), whose roles in specific functional responses is not fully understood. Elucidating the complexity and cross talks among signalling mediators involved in the TNFα-mediated responses will certainly aid in the identification of molecular targets, which can potentially lead to the development of novel therapeutics to treat TNFα-associated disorders and in dampening inflammation.

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Mishra, Prajna, Subramanian Senthivinayagam, Velusamy Rangasamy, Gautam Sondarva, and Basabi Rana. "Mixed Lineage Kinase-3/JNK1 Axis Promotes Migration of Human Gastric Cancer Cells following Gastrin Stimulation." Molecular Endocrinology 24, no. 3 (March 1, 2010): 598–607. http://dx.doi.org/10.1210/me.2009-0387.

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Abstract Gastrin is a gastrointestinal peptide hormone, secreted by the gastric G cells and can exist as a fully processed amidated form (G17) or as unprocessed forms. All forms of gastrin possess trophic properties towards the gastrointestinal mucosa. An understanding of the signaling pathways involved is important to design therapeutic approaches to target gastrin-mediated cellular events. The studies described here were designed to identify the signaling pathways by which amidated gastrin (G17) mediates cancer cell migration. These studies indicated a time- and dose-dependent increase in gastric cancer cell migration after G17 stimulation, involving cholecystokinin 2 receptor. G17-induced migration was preceded by activation of MAPK pathways and was antagonized after pretreatment with SP600125, a pharmacological inhibitor of c-Jun-NH2-terminal kinase (JNK) pathway. Knockdown of endogenous JNK1 expression via small interference RNA (JNK1-siRNA) inhibited G17-induced phosphorylation of c-Jun and migration, and overexpression of wild-type JNK1 or constitutive active JNK1 promoted G17-induced migration. Studies designed to identify the MAPK kinase kinase member mediating JNK activation indicated the involvement of mixed lineage kinase-3 (MLK3), which was transiently activated upon G17 treatment. Inhibition of MLK3 pathway via a pan-MLK inhibitor or knockdown of MLK3 expression by MLK3-siRNA antagonized G17-induced migration. Incubation with G17 also resulted in an induction of matrix metalloproteinase 7 promoter activity, which is known to mediate migration and invasion pathways in cancer cells. Modulation of MLK3, JNK1, and c-Jun pathways modulated G17-induced matrix metalloproteinase 7 promoter activation. These studies indicate that the MLK3/JNK1 axis mediates G17-induced gastric cancer cell migration, which can be targeted for designing novel therapeutic strategies for treating gastric malignancies.

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Wang, Haojie, Yumei Liu, Dongmei Wang, Yaolu Xu, Ruiqi Dong, Yuxiang Yang, Qiongxia Lv, Xiaoguang Chen, and Ziqiang Zhang. "The Upstream Pathway of mTOR-Mediated Autophagy in Liver Diseases." Cells 8, no. 12 (December 9, 2019): 1597. http://dx.doi.org/10.3390/cells8121597.

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Autophagy, originally found in liver experiments, is a cellular process that degrades damaged organelle or protein aggregation. This process frees cells from various stress states is a cell survival mechanism under stress stimulation. It is now known that dysregulation of autophagy can cause many liver diseases. Therefore, how to properly regulate autophagy is the key to the treatment of liver injury. mechanistic target of rapamycin (mTOR)is the core hub regulating autophagy, which is subject to different upstream signaling pathways to regulate autophagy. This review summarizes three upstream pathways of mTOR: the phosphoinositide 3-kinase (PI3K)/protein kinase (AKT) signaling pathway, the adenosine monophosphate-activated protein kinase (AMPK) signaling pathway, and the rat sarcoma (Ras)/rapidly accelerated fibrosarcoma (Raf)/mitogen-extracellular activated protein kinase kinase (MEK)/ extracellular-signal-regulated kinase (ERK) signaling pathway, specifically explored their role in liver fibrosis, hepatitis B, non-alcoholic fatty liver, liver cancer, hepatic ischemia reperfusion and other liver diseases through the regulation of mTOR-mediated autophagy. Moreover, we also analyzed the crosstalk between these three pathways, aiming to find new targets for the treatment of human liver disease based on autophagy.

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Skourtis, Spiros S., Chaoren Liu, Panayiotis Antoniou, Aaron M. Virshup, and David N. Beratan. "Dexter energy transfer pathways." Proceedings of the National Academy of Sciences 113, no. 29 (July 5, 2016): 8115–20. http://dx.doi.org/10.1073/pnas.1517189113.

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Energy transfer with an associated spin change of the donor and acceptor, Dexter energy transfer, is critically important in solar energy harvesting assemblies, damage protection schemes of photobiology, and organometallic opto-electronic materials. Dexter transfer between chemically linked donors and acceptors is bridge mediated, presenting an enticing analogy with bridge-mediated electron and hole transfer. However, Dexter coupling pathways must convey both an electron and a hole from donor to acceptor, and this adds considerable richness to the mediation process. We dissect the bridge-mediated Dexter coupling mechanisms and formulate a theory for triplet energy transfer coupling pathways. Virtual donor–acceptor charge-transfer exciton intermediates dominate at shorter distances or higher tunneling energy gaps, whereas virtual intermediates with an electron and a hole both on the bridge (virtual bridge excitons) dominate for longer distances or lower energy gaps. The effects of virtual bridge excitons were neglected in earlier treatments. The two-particle pathway framework developed here shows how Dexter energy-transfer rates depend on donor, bridge, and acceptor energetics, as well as on orbital symmetry and quantum interference among pathways.

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A Abdullah, Ashwaq, Rasedee Abdullah, Zeenathul A Nazariah, Krishnan N Balakrishnan, Faez Firdaus J Abdullah, Jamilu A Bala, and Mohd-Azmi Mohd-Lila. "Cyclophilin A as a target in the treatment of cytomegalovirus infections." Antiviral Chemistry and Chemotherapy 26 (January 2018): 204020661881141. http://dx.doi.org/10.1177/2040206618811413.

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Background Viruses are obligate parasites that depend on the cellular machinery of the host to regenerate and manufacture their proteins. Most antiviral drugs on the market today target viral proteins. However, the more recent strategies involve targeting the host cell proteins or pathways that mediate viral replication. This new approach would be effective for most viruses while minimizing drug resistance and toxicity. Methods Cytomegalovirus replication, latency, and immune response are mediated by the intermediate early protein 2, the main protein that determines the effectiveness of drugs in cytomegalovirus inhibition. This review explains how intermediate early protein 2 can modify the action of cyclosporin A, an immunosuppressive, and antiviral drug. It also links all the pathways mediated by cyclosporin A, cytomegalovirus replication, and its encoded proteins. Results Intermediate early protein 2 can influence the cellular cyclophilin A pathway, affecting cyclosporin A as a mediator of viral replication or anti-cytomegalovirus drug. Conclusion Cyclosporin A has a dual function in cytomegalovirus pathogenesis. It has the immunosuppressive effect that establishes virus replication through the inhibition of T-cell function. It also has an anti-cytomegalovirus effect mediated by intermediate early protein 2. Both of these functions involve cyclophilin A pathway.

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Wang, H., Y. Lee, and C. C. Malbon. "PDE6 is an effector for the Wnt/Ca2+/cGMP-signalling pathway in development." Biochemical Society Transactions 32, no. 5 (October 26, 2004): 792–96. http://dx.doi.org/10.1042/bst0320792.

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Wnt signalling in development operates via members of the Frizzleds, G-protein-coupled receptors that bind specific Wnt ligands and mediate signalling via distinct pathways. The Wnt/Ca2+/cGMP pathway mediated by Frizzled-2 was discovered recently. Activation of this pathway leads to increased intracellular concentrations of Ca2+ and decreased intracellular concentrations of cGMP. The nature of the phosphodiesterase responsible for this Frizzled-2-mediated effect on cGMP levels was identified based on three separate criteria: (i) sensitivity to selective enzyme inhibitors, (ii) behaviour on chromatographic separation, and (ii) isolation by two-dimensional gels in tandem with direct mapping by MS of tryptic digests of the activity. On the basis of results from these three analyses, the cGMP-specific phosphodiesterase, PDE6, is demonstrated to be an effector for the Wnt/Ca2+/cGMP signalling pathway of development, which is mediated by Frizzled-2.

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Yamaguchi, Masahiro, Kanako Miyano, Shigeto Hirayama, Yusuke Karasawa, Kaori Ohshima, Eiko Uezono, Akane Komatsu, et al. "Evaluation of the Intracellular Signaling Activities of κ-Opioid Receptor Agonists, Nalfurafine Analogs; Focusing on the Selectivity of G-Protein- and β-Arrestin-Mediated Pathways." Molecules 27, no. 20 (October 19, 2022): 7065. http://dx.doi.org/10.3390/molecules27207065.

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Opioid receptors (ORs) are classified into three types (μ, δ, and κ), and opioid analgesics are mainly mediated by μOR activation; however, their use is sometimes restricted by unfavorable effects. The selective κOR agonist nalfurafine was initially developed as an analgesic, but its indication was changed because of the narrow safety margin. The activation of ORs mainly induces two intracellular signaling pathways: a G-protein-mediated pathway and a β-arrestin-mediated pathway. Recently, the expectations for κOR analgesics that selectively activate these pathways have increased; however, the structural properties required for the selectivity of nalfurafine are still unknown. Therefore, we evaluated the partial structures of nalfurafine that are necessary for the selectivity of these two pathways. We assayed the properties of nalfurafine and six nalfurafine analogs (SYKs) using cells stably expressing κORs. The SYKs activated κORs in a concentration-dependent manner with higher EC50 values than nalfurafine. Upon bias factor assessment, only SYK-309 (possessing the 3S-hydroxy group) showed higher selectivity of G-protein-mediated signaling activities than nalfurafine, suggesting the direction of the 3S-hydroxy group may affect the β-arrestin-mediated pathway. In conclusion, nalfurafine analogs having a 3S-hydroxy group, such as SYK-309, could be considered G-protein-biased κOR agonists.

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Máthé, Csaba, Tamás Garda, Csongor Freytag, and Márta M-Hamvas. "The Role of Serine-Threonine Protein Phosphatase PP2A in Plant Oxidative Stress Signaling—Facts and Hypotheses." International Journal of Molecular Sciences 20, no. 12 (June 21, 2019): 3028. http://dx.doi.org/10.3390/ijms20123028.

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Abiotic and biotic factors induce oxidative stress involving the production and scavenging of reactive oxygen species (ROS). This review is a survey of well-known and possible roles of serine-threonine protein phosphatases in plant oxidative stress signaling, with special emphasis on PP2A. ROS mediated signaling involves three interrelated pathways: (i) perception of extracellular ROS triggers signal transduction pathways, leading to DNA damage and/or the production of antioxidants; (ii) external signals induce intracellular ROS generation that triggers the relevant signaling pathways and (iii) external signals mediate protein phosphorylation dependent signaling pathway(s), leading to the expression of ROS producing enzymes like NADPH oxidases. All pathways involve inactivation of serine-threonine protein phosphatases. The metal dependent phosphatase PP2C has a negative regulatory function during ABA mediated ROS signaling. PP2A is the most abundant protein phosphatase in eukaryotic cells. Inhibitors of PP2A exert a ROS inducing activity as well and we suggest that there is a direct relationship between these two effects of drugs. We present current findings and hypotheses regarding PP2A-ROS signaling connections related to all three ROS signaling pathways and anticipate future research directions for this field. These mechanisms have implications in the understanding of stress tolerance of vascular plants, having applications regarding crop improvement.

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Soo, Sonja K., Annika Traa, Paige D. Rudich, Meeta Mistry, and Jeremy M. Van Raamsdonk. "Activation of mitochondrial unfolded protein response protects against multiple exogenous stressors." Life Science Alliance 4, no. 12 (September 28, 2021): e202101182. http://dx.doi.org/10.26508/lsa.202101182.

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The mitochondrial unfolded protein response (mitoUPR) is an evolutionarily conserved pathway that responds to mitochondria insults through transcriptional changes, mediated by the transcription factor ATFS-1/ATF-5, which acts to restore mitochondrial homeostasis. In this work, we characterized the role of ATFS-1 in responding to organismal stress. We found that activation of ATFS-1 is sufficient to cause up-regulation of genes involved in multiple stress response pathways including the DAF-16–mediated stress response pathway, the cytosolic unfolded protein response, the endoplasmic reticulum unfolded protein response, the SKN-1–mediated oxidative stress response pathway, the HIF-1-mediated hypoxia response pathway, the p38-mediated innate immune response pathway, and antioxidant genes. Constitutive activation of ATFS-1 increases resistance to multiple acute exogenous stressors, whereas disruption of atfs-1 decreases stress resistance. Although ATFS-1–dependent genes are up-regulated in multiple long-lived mutants, constitutive activation of ATFS-1 decreases lifespan in wild-type animals. Overall, our work demonstrates that ATFS-1 serves a vital role in organismal survival of acute stressors through its ability to activate multiple stress response pathways but that chronic ATFS-1 activation is detrimental for longevity.

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Erdman, Laura, Gabriela Cosio, Samir N. Patel, Sergio Grinstein, and Kevin C. Kain. "Innate inflammatory and phagocytic responses to Plasmodium falciparum: linked processes or molecularly discrete pathways?s." Clinical & Investigative Medicine 30, no. 4 (August 1, 2007): 81. http://dx.doi.org/10.25011/cim.v30i4.2851.

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Background: Effective innate immune responses are important for control of malaria blood-stage infection and in preventing progression to severe malaria in non-immune individuals. Key innate defenses include a tightly regulated inflammatory response and host clearance of parasitized erythrocytes (PE). Pattern recognition receptors on macrophages mediate these processes: parasite glycosylphosphatidylinositol (GPI) activates TLR2 to induce inflammation – an excess of which is associated with severe malaria – while scavenger receptor CD36 mediates non-opsonic uptake of PEs. Both pathways are potential therapeutic targets, but it is unclear whether they are interdependent. Findings in other systems implicate CD36 in inflammation and TLR2 in phagocytosis, and recent evidence indicates that CD36 and TLR2 can directly cooperate. Methods: We investigated whether the innate inflammatory and phagocytic responses of macrophages to P. falciparum are separable: does CD36-mediated PE internalization have inflammatory outcomes, and does TLR2 regulate PE uptake? CD36-mediated endocytosis failed to induce TNFα production. As a more representative model of innate PE uptake, α-CD36 EBABs (Erythrocyte-Biotin-Avidin-Biotinylated antibody) were generated; macrophages internalized EBABs in a CD36-specific manner via a signaling pathway similar to that of PE uptake. Results: Compared to controls, neither PE nor EBAB internalization induced TNFα release, indicating that the inflammatory consequences of CD36 engagement are ligand dependent. Regarding TLR2 regulation of PE uptake, wild type and Tlr2-/- macrophages showed no differences in EBAB or PE uptake. Pre-treatment of macrophages with P. falciparum GPI enhanced EBAB internalization, but this effect was CD36-independent and generalizable to other TLR ligands. Conclusions: These results suggest that innate inflammatory and phagocytic responses of macrophages to malaria are discrete. Thus, therapeutic augmentation of CD36-mediated PE uptake should not exacerbate inflammation, nor should inhibition of the TLR2 pathway compromise CD36-mediated PE clearance. The role of TLR-enhanced internalization in malaria will be further examined.

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Insall, R. H., R. D. Soede, P. Schaap, and P. N. Devreotes. "Two cAMP receptors activate common signaling pathways in Dictyostelium." Molecular Biology of the Cell 5, no. 6 (June 1994): 703–11. http://dx.doi.org/10.1091/mbc.5.6.703.

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Multiple signal transduction pathways within a single cell may share common components. In particular, seven different transmembrane helix receptors may activate identical pathways by interacting with the same G-proteins. Dictyostelium cells respond to cAMP using one such receptor, cAR1, coupled by a typical heterotrimeric G-protein to intracellular effectors. However, cells in which the gene for cAR1 has been deleted are unexpectedly still able to respond to cAMP. This implies either that certain responses are mediated by a different receptor than cAR1, or alternatively that a second, partially redundant receptor shares some of the functions of cAR1. We have examined the dose response and ligand specificity of one response, cAMP relay, and the dose response of another, cyclic GMP synthesis. In each case, the EC50 was approximately 100-fold higher and the maximal response was smaller in car1- than wild-type cells. These data indicate that cAR1 normally mediates responses to cAMP. The ligand specificity suggests that the responses seen in car1- mutants are mediated by a second receptor, cAR3. To test this hypothesis, we constructed a cell line containing deletions of both cAR1 and cAR3 genes. As predicted, these lines are totally insensitive to cAMP. We conclude that the functions of the cAR1 and cAR3 receptors are partially redundant and that both interact with the same heterotrimeric G-protein to mediate these and other responses.

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Catarino, Steve, Paulo Pereira, and Henrique Girão. "Molecular control of chaperone-mediated autophagy." Essays in Biochemistry 61, no. 6 (December 12, 2017): 663–74. http://dx.doi.org/10.1042/ebc20170057.

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Chaperone-mediated autophagy (CMA) is a selective form of autophagy in which cytosolic proteins bearing a pentapeptide motif biochemically related to the KFERQ sequence, are recognized by the heat shock protein family A member 8 (HSPA8) chaperone, delivered to the lysomal membrane, and directly translocated across the lysosomal membrane by a protein complex containing lysosomal associated membrane protein 2a (Lamp2a). Since its discovery over two decades ago, the importance of this pathway in cell proteostasis has been made increasingly apparent. Deregulation of this pathway has been implicated in a variety of diseases and conditions, including lysosomal storage diseases, cancer, neurodegeneration and even aging. Here, we describe the main molecular features of the pathway, its regulation, cross-talk with other degradation pathways and importance in disease.

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Shi, Yufeng, Christopher J. Stefan, Sarah M. Rue, David Teis, and Scott D. Emr. "Two novel WD40 domain–containing proteins, Ere1 and Ere2, function in the retromer-mediated endosomal recycling pathway." Molecular Biology of the Cell 22, no. 21 (November 2011): 4093–107. http://dx.doi.org/10.1091/mbc.e11-05-0440.

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Regulated secretion, nutrient uptake, and responses to extracellular signals depend on cell-surface proteins that are internalized and recycled back to the plasma membrane. However, the underlying mechanisms that govern membrane protein recycling to the cell surface are not fully known. Using a chemical-genetic screen in yeast, we show that the arginine transporter Can1 is recycled back to the cell surface via two independent pathways mediated by the sorting nexins Snx4/41/42 and the retromer complex, respectively. In addition, we identify two novel WD40-domain endosomal recycling proteins, Ere1 and Ere2, that function in the retromer pathway. Ere1 is required for Can1 recycling via the retromer-mediated pathway, but it is not required for the transport of other retromer cargoes, such as Vps10 and Ftr1. Biochemical studies reveal that Ere1 physically interacts with internalized Can1. Ere2 is present in a complex containing Ere1 on endosomes and functions as a regulator of Ere1. Taken together, our results suggest that Snx4/41/42 and the retromer comprise two independent pathways for the recycling of internalized cell-surface proteins. Moreover, a complex containing the two novel proteins Ere1 and Ere2 mediates cargo-specific recognition by the retromer pathway.

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Piovia-Scott, Jonah, David A. Spiller, Gaku Takimoto, Louie H. Yang, Amber N. Wright, and Thomas W. Schoener. "The effect of chronic seaweed subsidies on herbivory: plant-mediated fertilization pathway overshadows lizard-mediated predator pathways." Oecologia 172, no. 4 (March 19, 2013): 1129–35. http://dx.doi.org/10.1007/s00442-012-2560-0.

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Sun, Tong, and Leung Kim. "Tyrosine Phosphorylation-Mediated Signaling Pathways in Dictyostelium." Journal of Signal Transduction 2011 (April 14, 2011): 1–7. http://dx.doi.org/10.1155/2011/894351.

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While studies on metazoan cell proliferation, cell differentiation, and cytokine signaling laid the foundation of the current paradigms of tyrosine kinase signaling, similar studies using lower eukaryotes have provided invaluable insight for the understanding of mammalian pathways, such as Wnt and STAT pathways. Dictyostelium is one of the leading lower eukaryotic model systems where stress-induced cellular responses, Wnt-like pathways, and STAT-mediated pathways are well investigated. These Dictyostelium pathways will be reviewed together with their mammalian counterparts to facilitate the comparative understanding of these variant and noncanonical pathways.

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Mishra, Pankaj, Mark Palma, Ariel Millman, Nadim Hallab, Kathleen Beebe, Joseph Benevenia, and William Gause. "Blockade of either SYK or BTK signaling pathways inhibits microparticle-induced type 2 inflammatory response (IRM11P.628)." Journal of Immunology 194, no. 1_Supplement (May 1, 2015): 132.7. http://dx.doi.org/10.4049/jimmunol.194.supp.132.7.

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Abstract Wear debris microparticle release associated with total joint arthroplasty may contribute to harmful inflammation, osteolysis and implant failure. We examined the role of different molecular signaling pathways in microparticle-mediated inflammation. Intraperitoneal inoculation of cobalt chrome (CoCr) in mice induced a robust innate type 2 response with increases in Th2 cytokines, M2 macrophages, eosinophils and neutrophils compared to controls given vehicle only. Furthermore, this type 2 innate particle-induced response was independent of MYD88/TRIF and partially dependent on Caspase-1 signaling pathways. Blockade of the PGE-2 signaling pathway by administration of Aspirin or Celecoxib prior to CoCr inoculation caused a significant reduction in both neutrophils and macrophages with no effect on eosinophils and Th2 cytokines compared to the mice treated with CoCr + vehicle. Blockade of the SYK signaling pathway with the inhibitor BAY61-3606 or the BTK signaling pathway with Ibrutinib completely abrogated the CoCr-mediated innate inflammation and Th2 cytokines. These studies indicate that the type 2 immune response caused by solid particles is partially modulated by Caspase-1 and PGE-2 pathways and largely abrogated by blockade of upstream SYK and BTK signaling pathways. These studies provide potential targets for controlling the wear debris-mediated inflammation in synovial tissues that can contribute to aseptic loosening and implant failure.

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Roifman, C. M., and G. Wang. "Receptor-mediated activation of human B lymphocytes in a nonphosphotyrosine-dependent manner." Journal of Immunology 149, no. 4 (August 15, 1992): 1179–84. http://dx.doi.org/10.4049/jimmunol.149.4.1179.

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Abstract The B cell AgR regulates two signal transduction pathways: the tyrosine kinase and the phosphatidylinositol (PtdIns) pathways. Stimulation of B cells with Ag or anti-Ig antibody results in a rapid increase in tyrosine phosphorylation of multiple substrates. The AgR also mediates the activation of phospholipase C-gamma 1 (PLC-gamma 1) thus producing the second messengers, inositol trisphosphate and diacylglycerol. Although the detailed relationship between these two signaling pathways remains unclear, it has recently become apparent that PLC-gamma 1 might be a target for the AgR-associated protein tyrosine kinase. To address the question of whether tyrosine kinase activity is essential for B cell activation, we studied early biochemical changes and later cellular events induced by ligation of the purinoceptor (P2R). Ligation of ATP to its receptor on B cells has been previously shown to elicit increases in cytosolic free Ca2+ and inositol phosphate production as well as induction of c-fos mRNA expression and increased expression of IL-2 and transferrin receptors. We show here that ATP in a wide range of concentrations did not increase protein tyrosine kinase activity. In contrast with the AgR, P2R did not mediate tyrosine phosphorylation of PLC-gamma 1, thus suggesting that it may use another phosphoinositide-specific PLC that does not require phosphorylation on tyrosine residues for its activation. The results were supported by experiments with a specific tyrosine kinase inhibitor, tyrphostin AG-126. Preincubation with this inhibitor blocked AgR but not P2R-mediated inositol phosphate production, cytosolic free Ca2+ changes, and IL-2 and transferrin receptor expression. The results indicate that the PtdIns pathway may be sufficient to induce activation of B cells and that the tyrosine phosphorylation pathway is not necessary for nonantigenic B cell activation.

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Chadani, Yuhei, Katsuhiko Ono, Kazuhiro Kutsukake, and Tatsuhiko Abo. "Escherichia coli YaeJ protein mediates a novel ribosome-rescue pathway distinct from SsrA- and ArfA-mediated pathways." Molecular Microbiology 80, no. 3 (March 21, 2011): 772–85. http://dx.doi.org/10.1111/j.1365-2958.2011.07607.x.

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Monteleone, Giovanni, Francesco Pallone, and Thomas T. Macdonald. "Interleukin-21 (IL-21)-mediated pathways in T cell-mediated disease." Cytokine & Growth Factor Reviews 20, no. 2 (April 2009): 185–91. http://dx.doi.org/10.1016/j.cytogfr.2009.02.002.

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Zhang, Zhenhua, Chenjie Xu, Shiyu Zhang, Chen Shi, Hong Cheng, Hongtao Liu, and Bojian Zhong. "Origin and adaptive evolution of UV RESISTANCE LOCUS 8-mediated signaling during plant terrestrialization." Plant Physiology 188, no. 1 (October 18, 2021): 332–46. http://dx.doi.org/10.1093/plphys/kiab486.

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Abstract UV RESISTANCE LOCUS 8 (UVR8) mediates photomorphogenic responses and acclimation to UV-B radiation by regulating the transcription of a series of transcription factors (TFs). However, the origin and evolution of UVR8-mediated signaling pathways remain largely unknown. In this study, we investigated the origin and evolution of the major components of the UVR8-mediated signaling pathway (UVR8, REPRESSOR OF UV-B PHOTOMORPHOGENESIS [RUP], BRI1-EMS-SUPPRESSOR1 [BES1], BES1-INTERACTING MYC-LIKE 1 (BIM1), WRKY DNA-BINDING PROTEIN 36 (WRKY36), MYB DOMAIN PROTEIN 73/77/13 [MYB73/MYB77/MYB13], and PHYTOCHROME INTERACTING FACTOR 4/5 [PIF4 and PIF5]) using comparative genomics and phylogenetic approaches. We showed that the central regulator UVR8 presented a conservative evolutionary route during plant evolution, and the evolutionary history of downstream negative regulators and TFs was different from that of green plant phylogeny. The canonical UVR8-CONSTITUTIVELY PHOTOMORPHOGENIC 1(COP1)/SUPPRESSOR OF PHYA-105 (SPA)-ELONGATED HYPOCOTYL 5 (HY5)-RUP signaling pathway originated in chlorophytes and conferred green algae the additional ability to cope with UV-B radiation. Moreover, the emergence of multiple UVR8-mediated signaling pathways in charophytes laid the foundations for the cross-talk between UV-B signals and endogenous hormone responses. Importantly, we observed signatures that reflect plant adaptations to high UV-B irradiance in subaerial/terrestrial environments, including positive selection in UVR8 and RUPs and increased copy number of some vital TFs. These results revealed that green plants not only experienced adaptive modifications in the canonical UVR8-COP1/SPA-HY5-RUP signaling pathway, but also diversified their UV-B signal transduction mechanisms through increasing cross-talk with other pathways, such as those associated with brassinosteroids and auxin. This study greatly expands our understanding of molecular evolution and adaptive mechanisms underlying plant UV-B acclimation.

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Lutkewitte, Andrew J., and Brian N. Finck. "Regulation of Signaling and Metabolism by Lipin-mediated Phosphatidic Acid Phosphohydrolase Activity." Biomolecules 10, no. 10 (September 29, 2020): 1386. http://dx.doi.org/10.3390/biom10101386.

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Phosphatidic acid (PA) is a glycerophospholipid intermediate in the triglyceride synthesis pathway that has incredibly important structural functions as a component of cell membranes and dynamic effects on intracellular and intercellular signaling pathways. Although there are many pathways to synthesize and degrade PA, a family of PA phosphohydrolases (lipin family proteins) that generate diacylglycerol constitute the primary pathway for PA incorporation into triglycerides. Previously, it was believed that the pool of PA used to synthesize triglyceride was distinct, compartmentalized, and did not widely intersect with signaling pathways. However, we now know that modulating the activity of lipin 1 has profound effects on signaling in a variety of cell types. Indeed, in most tissues except adipose tissue, lipin-mediated PA phosphohydrolase activity is far from limiting for normal rates of triglyceride synthesis, but rather impacts critical signaling cascades that control cellular homeostasis. In this review, we will discuss how lipin-mediated control of PA concentrations regulates metabolism and signaling in mammalian organisms.

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Wong, Fred, Christopher Hull, Rachel Zhande, Jennifer Law, and Aly Karsan. "Lipopolysaccharide initiates a TRAF6-mediated endothelial survival signal." Blood 103, no. 12 (June 15, 2004): 4520–26. http://dx.doi.org/10.1182/blood-2003-06-2118.

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Abstract Similar to tumor necrosis factor (TNF), bacterial lipopolysaccharide (LPS) elicits parallel apoptotic and antiapoptotic pathways in endothelial cells. The overall result is that there is minimal endothelial cell death in response to LPS without inhibition of the cytoprotective pathway. While the TNF-induced death and survival pathways have been relatively well elucidated, much remains to be learned about LPS signaling events in this regard. It is known that the transcription factor nuclear factor-κB (NF-κB) provides a critical cell survival signal in response to TNF, but is not an essential component of the LPS-induced survival pathway. The TNF receptor-associated factor 6 (TRAF6) is a major effector of multiple LPS-induced signals, including a c-Jun N-terminal kinase (JNK)-mediated apoptotic response. In this report we demonstrate that following LPS stimulation, TRAF6 also transmits an important endothelial cell survival signal in a situation of complete NF-κB blockade. In response to LPS, TRAF6 activates the phosphatidylinositol 3′-kinase (PI3K)/Akt pathway, but not ERK1/2 mitogen-activated protein kinases (MAPKs) in endothelial cells. Activation of PI3K signals a critical antiapoptotic pathway in response to LPS in endothelial cells, whereas ERK1/2 does not. Thus TRAF6 acts as a bifurcation point of the LPS-initiated death and survival signals in endothelial cells. (Blood. 2004;103:4520-4526)

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Journal articles on the topic 'Mediated pathways'

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