Oncostatin M signaling pathway (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 cell types such as activated T lymphocytes, macrophages, monocytes, neutrophils and in 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 lacks 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 induced the activation of caspase family members (CASP3, CASP7, CASP9) through the JAK2 module and regulates apoptosis [Auernhammer, Tiffen, Chipoy]. In osteosarcoma cells OSM is found to mediate apoptosis through a less understood STAT5B signaling module [Chipoy].
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- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
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