Oncostatin M signaling (Homo sapiens)
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Description
Oncostatin M (OSM) is a member of the multifunctional cytokine interleukin 6 (IL6) - type cytokine family. It is mainly produced in activated T lymphocytes, macrophages, monocytes, neutrophils, and microglial cells. OSM signaling is initiated by the interaction of the cytokine to either: the type I LIFR-gp130 receptor complex, or to the type II OSMR-gp130 receptor (O’Hara et al). The major downstream signaling pathways that are activated in OSM signaling are JAK/STAT, Ras/Raf/MAPK and PI3K pathways (Halfter, Halfter, Stross, Brantley). As the receptors lack intrinsic tyrosine kinase activity, associated JAKs (JAK1, JAK2, JAK3 and TYK2) phosphorylate OSM receptor complex and STATs (STAT1, STAT3, STAT5A, STAT5B, STAT6) (O’Hara, Fritz, Migita, Hintzen). Phosphorylated STATs form homodimeric complexes (STAT1, STAT3, STAT5B) or heterodimeric complex (STAT1-STAT3) and translocate to the nucleus. Once inside nucleus STAT proteins bind to regulatory elements in the promoter of OSM-responsive genes and regulate the gene expression (O’Hara, Halfter, Halfter, Hintzen). Alternatively, OSM induced phosphorylation of PTPN11, GRB2, SHC1, Ras/Raf molecules can bring about the activation of ERK1/2 signaling module (O’Hara). Oncostatin M -through ERK1/2 signaling module induces the phosphorylation of CEBPB, both CEBPB and EGR1 stimulates the transcription of genes involved in lipid metabolism (Zhang). Although OSM also causes induced phosphorylation in MAPK family members (MAPK8/9/14) the functional importance of this is at present not well understood (O’Hara, Li). OSM mediated signaling cascade is negatively regulated by JAK1 inhibition by SOCS3 and STAT3 inhibition by PIAS3 (Stross, Brantley, Chung). OSM also induces the activation of caspase family members (CASP3, CASP7, CASP9) through the JAK2 module and regulates apoptosis (Auernhammer, Tiffen, Chipoy). In osteosarcoma cells, OSM mediates apoptosis through a less understood STAT5B signaling module (Chipoy).
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Bibliography
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- Halfter H, Postert C, Friedrich M, Ringelstein EB, Stögbauer F; ''Activation of the Jak-Stat- and MAPK-pathways by oncostatin M is not sufficient to cause growth inhibition of human glioma cells.''; Brain Res Mol Brain Res, 2000 PubMed Europe PMC Scholia
- Stross C, Radtke S, Clahsen T, Gerlach C, Volkmer-Engert R, Schaper F, Heinrich PC, Hermanns HM; ''Oncostatin M receptor-mediated signal transduction is negatively regulated by SOCS3 through a receptor tyrosine-independent mechanism.''; J Biol Chem, 2006 PubMed Europe PMC Scholia
- Brantley EC, Benveniste EN; ''Signal transducer and activator of transcription-3: a molecular hub for signaling pathways in gliomas.''; Mol Cancer Res, 2008 PubMed Europe PMC Scholia
- Fritz DK, Kerr C, Tong L, Smyth D, Richards CD; ''Oncostatin-M up-regulates VCAM-1 and synergizes with IL-4 in eotaxin expression: involvement of STAT6.''; J Immunol, 2006 PubMed Europe PMC Scholia
- Chung CD, Liao J, Liu B, Rao X, Jay P, Berta P, Shuai K; ''Specific inhibition of Stat3 signal transduction by PIAS3.''; Science, 1997 PubMed Europe PMC Scholia
- Hintzen C, Evers C, Lippok BE, Volkmer R, Heinrich PC, Radtke S, Hermanns HM; ''Box 2 region of the oncostatin M receptor determines specificity for recruitment of Janus kinases and STAT5 activation.''; J Biol Chem, 2008 PubMed Europe PMC Scholia
- Auernhammer CJ, Dorn F, Vlotides G, Hengge S, Kopp FB, Spoettl G, Cengic N, Engelhardt D, Weber MM; ''The oncostatin M receptor/gp130 ligand murine oncostatin M induces apoptosis in adrenocortical Y-1 tumor cells.''; J Endocrinol, 2004 PubMed Europe PMC Scholia
- Migita K, Komori A, Torigoshi T, Maeda Y, Izumi Y, Jiuchi Y, Miyashita T, Nakamura M, Motokawa S, Ishibashi H; ''CP690,550 inhibits oncostatin M-induced JAK/STAT signaling pathway in rheumatoid synoviocytes.''; Arthritis Res Ther, 2011 PubMed Europe PMC Scholia
- O'Hara KA, Kedda MA, Thompson PJ, Knight DA; ''Oncostatin M: an interleukin-6-like cytokine relevant to airway remodelling and the pathogenesis of asthma.''; Clin Exp Allergy, 2003 PubMed Europe PMC Scholia
- Li WQ, Dehnade F, Zafarullah M; ''Oncostatin M-induced matrix metalloproteinase and tissue inhibitor of metalloproteinase-3 genes expression in chondrocytes requires Janus kinase/STAT signaling pathway.''; J Immunol, 2001 PubMed Europe PMC Scholia
- Chipoy C, Brounais B, Trichet V, Battaglia S, Berreur M, Oliver L, Juin P, Rédini F, Heymann D, Blanchard F; ''Sensitization of osteosarcoma cells to apoptosis by oncostatin M depends on STAT5 and p53.''; Oncogene, 2007 PubMed Europe PMC Scholia
- Halfter H, Friedrich M, Postert C, Ringelstein EB, Stögbauer F; ''Activation of Jak-Stat and MAPK2 pathways by oncostatin M leads to growth inhibition of human glioma cells.''; Mol Cell Biol Res Commun, 1999 PubMed Europe PMC Scholia
- Zhang F, Lin M, Abidi P, Thiel G, Liu J; ''Specific interaction of Egr1 and c/EBPbeta leads to the transcriptional activation of the human low density lipoprotein receptor gene.''; J Biol Chem, 2003 PubMed Europe PMC Scholia
- Tiffen PG, Omidvar N, Marquez-Almuina N, Croston D, Watson CJ, Clarkson RW; ''A dual role for oncostatin M signaling in the differentiation and death of mammary epithelial cells in vivo.''; Mol Endocrinol, 2008 PubMed Europe PMC Scholia
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