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]. f58 a3d c86 cf4 cbe b55 dcd a74 e1d d70 d40 ebc f72 ada 15012602 PubMed The oncostatin M receptor/gp130 ligand murine oncostatin M induces apoptosis in adrenocortical Y-1 tumor cells. J Endocrinol 2004 Auernhammer CJ Dorn F Vlotides G Hengge S Kopp FB Spoettl G Cengic N Engelhardt D Weber MM 12947119 PubMed Specific interaction of Egr1 and c/EBPbeta leads to the transcriptional activation of the human low density lipoprotein receptor gene. J Biol Chem 2003 Zhang F Lin M Abidi P Thiel G Liu J 21548952 PubMed CP690,550 inhibits oncostatin M-induced JAK/STAT signaling pathway in rheumatoid synoviocytes. Arthritis Res Ther 2011 Migita K Komori A Torigoshi T Maeda Y Izumi Y Jiuchi Y Miyashita T Nakamura M Motokawa S Ishibashi H 17471233 PubMed Sensitization of osteosarcoma cells to apoptosis by oncostatin M depends on STAT5 and p53. Oncogene 2007 Chipoy C Brounais B Trichet V Battaglia S Berreur M Oliver L Juin P Rédini F Heymann D Blanchard F 18505913 PubMed Signal transducer and activator of transcription-3: a molecular hub for signaling pathways in gliomas. Mol Cancer Res 2008 Brantley EC Benveniste EN 16459330 PubMed Oncostatin M receptor-mediated signal transduction is negatively regulated by SOCS3 through a receptor tyrosine-independent mechanism. J Biol Chem 2006 Stross C Radtke S Clahsen T Gerlach C Volkmer-Engert R Schaper F Heinrich PC Hermanns HM 18927239 PubMed A dual role for oncostatin M signaling in the differentiation and death of mammary epithelial cells in vivo. Mol Endocrinol 2008 Tiffen PG Omidvar N Marquez-Almuina N Croston D Watson CJ Clarkson RW 9388184 PubMed Specific inhibition of Stat3 signal transduction by PIAS3. Science 1997 Chung CD Liao J Liu B Rao X Jay P Berta P Shuai K oncostatin M signaling pathway PW:0000905 Pathway Ontology 16547273 PubMed Oncostatin-M up-regulates VCAM-1 and synergizes with IL-4 in eotaxin expression: involvement of STAT6. J Immunol 2006 Fritz DK Kerr C Tong L Smyth D Richards CD 12911774 PubMed Oncostatin M: an interleukin-6-like cytokine relevant to airway remodelling and the pathogenesis of asthma. Clin Exp Allergy 2003 O'Hara KA Kedda MA Thompson PJ Knight DA 11038252 PubMed 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 Halfter H Postert C Friedrich M Ringelstein EB Stögbauer F 11207308 PubMed Oncostatin M-induced matrix metalloproteinase and tissue inhibitor of metalloproteinase-3 genes expression in chondrocytes requires Janus kinase/STAT signaling pathway. J Immunol 2001 Li WQ Dehnade F Zafarullah M 10356359 PubMed Activation of Jak-Stat and MAPK2 pathways by oncostatin M leads to growth inhibition of human glioma cells. Mol Cell Biol Res Commun 1999 Halfter H Friedrich M Postert C Ringelstein EB Stögbauer F 18430728 PubMed Box 2 region of the oncostatin M receptor determines specificity for recruitment of Janus kinases and STAT5 activation. J Biol Chem 2008 Hintzen C Evers C Lippok BE Volkmer R Heinrich PC Radtke S Hermanns HM