Oncostatin M Signaling Pathway (Homo sapiens)
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Description
OSM mediated stimulation of its receptors, causes the activation of downstream signaling cascades. JAK/STAT, Ras/Raf/MAPK and PI 3-kinase through phosphorylation . On phosphorylation the STATs undergo homo- or hetero-dimerization, followed by their nuclear translocation and subsequent regulation of target gene expression . The dual effects of OSM, is mediated through the variation in phosphorylation of residues at selected sites, in different cell types or conditions. The OSM stimulation of JAK/STAT/PI 3 K leads to the increased expression of SOCS3 mRNA . The increased SOCS3 expression in turn effects the inactivation of JAK1, upon OSM stimulation.
1. Auguste, P., et al., Signaling of type II oncostatin M receptor. J Biol Chem, 1997. 272(25): p. 15760-4. 2. !!! INVALID CITATION !!! 3. Blanchard, F., et al., Oncostatin M regulates the synthesis and turnover of gp130, leukemia inhibitory factor receptor alpha, and oncostatin M receptor beta by distinct mechanisms. J Biol Chem, 2001. 276(50): p. 47038-45. 4. Li, W.Q., F. Dehnade, and M. Zafarullah, Oncostatin M-induced matrix metalloproteinase and tissue inhibitor of metalloproteinase-3 genes expression in chondrocytes requires Janus kinase/STAT signaling pathway. J Immunol, 2001. 166(5): p. 3491-8. 5. Lin, S.K., et al., MEK/ERK and signal transducer and activator of transcription signaling pathways modulate oncostatin M-stimulated CCL2 expression in human osteoblasts through a common transcription factor. Arthritis Rheum, 2004. 50(3): p. 785-93. 6. Halfter, H., et al., 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. 80(2): p. 198-206. 7. Hintzen, C., et al., Box 2 region of the oncostatin M receptor determines specificity for recruitment of Janus kinases and STAT5 activation. J Biol Chem, 2008. 283(28): p. 19465-77. 8. Ihn, H. and K. Tamaki, Oncostatin M stimulates the growth of dermal fibroblasts via a mitogen-activated protein kinase-dependent pathway. J Immunol, 2000. 165(4): p. 2149-55. 9. Mahboubi, K., et al., Desensitization of signaling by oncostatin M in human vascular cells involves cytoplasmic Tyr residue 759 in gp130 but is not mediated by either Src homology 2 domain-containing tyrosine phosphatase 2 or suppressor of cytokine signaling 3. J Biol Chem, 2003. 278(27): p. 25014-23.
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