Oncostatin-M

Functions as a cytokine that uses both type I OSM receptor (heterodimers composed of LIFR and IL6ST) and type II OSM receptor (heterodimers composed of OSMR and IL6ST) (PubMed:10997905, PubMed:39532904, PubMed:8999038). Functionally, regulates many processes including cell proliferation, cell differentiation, cytokine production (PubMed:10997905, PubMed:1542792, PubMed:1542793, PubMed:1717982, PubMed:2779549, PubMed:3540948). Mechanistically, low affinity ligand binding to IL6ST/gp130, induces heterodimerization with LIFR or OSMR, activating JAK tyrosine kinases (JAK1 or JAK2 and to a lesser extent TYK2) bound to their intracellular domains (PubMed:9188471). These kinases subsequently phosphorylate IL6ST/gp130 and LIFR or OSMR (PubMed:8999038). The tyrosine phosphorylated signaling receptors serve in turn as docking sites for recruitment and activation of STAT3 (PubMed:9188471). The type II OSM complex receptor is also able in addition to STAT3 to recruit STAT5B (PubMed:9188471). Moreover, the type II OSM complex receptor recruits SHC1 through OSMR in a JAK1 mediated phosphotyrosine-dependent manner, leading to SHC1 association with GRB2 and downstream activation of the Ras/Raf/MAPK pathway (PubMed:11016927)