Oncostatin M signaling (WP2374)

Homo sapiens

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].


NetPath , Kristina Hanspers , Daniela Digles , Martina Summer-Kutmon , Alex Pico , Mechebek Maghnaui , Eric Weitz , and Egon Willighagen


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Homo sapiens



Pathway Ontology

oncostatin M signaling pathway


Label Type Compact URI Comment
HIF1A GeneProduct ensembl:ENSG00000100644
VEGFA GeneProduct ensembl:ENSG00000112715
JUND Protein ncbigene:3727
KRAS Protein ncbigene:3845
MAPK9 Protein ncbigene:5601
MAPK8 Protein ncbigene:5599
MAP2K1 Protein ncbigene:5604
LIFR Protein ncbigene:3977
JAK2 Protein ncbigene:3717
PRKCH Protein ncbigene:5583
PRKCE Protein ncbigene:5581
PRKCB Protein ncbigene:5579
PRKCA Protein ncbigene:5578
IL6ST Protein ncbigene:3572
MAP2K2 Protein ncbigene:5605
STAT3 Protein ncbigene:6774
STAT1 Protein ncbigene:6772
IL6ST Protein ncbigene:3572
JAK1 Protein ncbigene:3716
MAPK14 Protein ncbigene:1432
JAK3 Protein ncbigene:3718
TYK2 Protein ncbigene:7297
RELA Protein ncbigene:5970
MAPK3 Protein ncbigene:5595
SOCS3 Protein ncbigene:9021
OSMR Protein ncbigene:9180
PTPN11 Protein ncbigene:5781
MAPK1 Protein ncbigene:5594
STAT1 Protein ncbigene:6772
PIAS3 Protein ncbigene:10401
STAT5B Protein ncbigene:6777
STAT5B Protein ncbigene:6777
CASP3 Protein ncbigene:836
OSM Protein ncbigene:5008
SOS1 Protein ncbigene:6654
GRB2 Protein ncbigene:2885
SHC1 Protein ncbigene:6464
IRS1 Protein ncbigene:3667
SRC Protein ncbigene:6714
STAT3 Protein ncbigene:6774
RAF1 Protein ncbigene:5894
HRAS Protein ncbigene:3265
PIK3R1 Protein ncbigene:5295
AKT1 Protein ncbigene:207
OSM Protein ncbigene:5008
STAT3 Protein ncbigene:6774
STAT1 Protein ncbigene:6772
FOS Protein ncbigene:2353
PXN Protein ncbigene:5829
PTK2B Protein ncbigene:2185
CDK2 Protein ncbigene:1017
CDKN1B Protein ncbigene:1027
CEBPB Protein ncbigene:1051
RPS6 Protein ncbigene:6194
JUNB Protein ncbigene:3726
STAT3 Protein ncbigene:6774
PRKCD Protein ncbigene:5580
MTOR Protein ncbigene:2475
STAT1 Protein ncbigene:6772
STAT5B Protein ncbigene:6777
RICTOR Protein ncbigene:253260
CREB1 Protein ncbigene:1385
EGR1 Protein ncbigene:1958
NFKB1 Protein ncbigene:4790
NFKBIA Protein ncbigene:4792
RELA Protein ncbigene:5970
NFKB1 Protein ncbigene:4790
STAT5B Protein ncbigene:6777
STAT3 Protein ncbigene:6774
STAT1 Protein ncbigene:6772
MAPK3 Protein ncbigene:5595
MAPK1 Protein ncbigene:5594
CASP7 Protein ncbigene:840
CASP9 Protein ncbigene:840


  1. Specific inhibition of Stat3 signal transduction by PIAS3. Chung CD, Liao J, Liu B, Rao X, Jay P, Berta P, et al. Science. 1997 Dec 5;278(5344):1803–5. PubMed Europe PMC Scholia
  2. Activation of Jak-Stat and MAPK2 pathways by oncostatin M leads to growth inhibition of human glioma cells. Halfter H, Friedrich M, Postert C, Ringelstein EB, Stögbauer F. Mol Cell Biol Res Commun. 1999 May;1(2):109–16. PubMed Europe PMC Scholia
  3. Activation of the Jak-Stat- and MAPK-pathways by oncostatin M is not sufficient to cause growth inhibition of human glioma cells. Halfter H, Postert C, Friedrich M, Ringelstein EB, Stögbauer F. Brain Res Mol Brain Res. 2000 Sep 15;80(2):198–206. PubMed Europe PMC Scholia
  4. Oncostatin M-induced matrix metalloproteinase and tissue inhibitor of metalloproteinase-3 genes expression in chondrocytes requires Janus kinase/STAT signaling pathway. Li WQ, Dehnade F, Zafarullah M. J Immunol. 2001 Mar 1;166(5):3491–8. PubMed Europe PMC Scholia
  5. Oncostatin M: an interleukin-6-like cytokine relevant to airway remodelling and the pathogenesis of asthma. O’Hara KA, Kedda MA, Thompson PJ, Knight DA. Clin Exp Allergy. 2003 Aug;33(8):1026–32. PubMed Europe PMC Scholia
  6. Specific interaction of Egr1 and c/EBPbeta leads to the transcriptional activation of the human low density lipoprotein receptor gene. Zhang F, Lin M, Abidi P, Thiel G, Liu J. J Biol Chem. 2003 Nov 7;278(45):44246–54. PubMed Europe PMC Scholia
  7. The oncostatin M receptor/gp130 ligand murine oncostatin M induces apoptosis in adrenocortical Y-1 tumor cells. Auernhammer CJ, Dorn F, Vlotides G, Hengge S, Kopp FB, Spoettl G, et al. J Endocrinol. 2004 Mar;180(3):479–86. PubMed Europe PMC Scholia
  8. Oncostatin M receptor-mediated signal transduction is negatively regulated by SOCS3 through a receptor tyrosine-independent mechanism. Stross C, Radtke S, Clahsen T, Gerlach C, Volkmer-Engert R, Schaper F, et al. J Biol Chem. 2006 Mar 31;281(13):8458–68. PubMed Europe PMC Scholia
  9. Oncostatin-M up-regulates VCAM-1 and synergizes with IL-4 in eotaxin expression: involvement of STAT6. Fritz DK, Kerr C, Tong L, Smyth D, Richards CD. J Immunol. 2006 Apr 1;176(7):4352–60. PubMed Europe PMC Scholia
  10. Sensitization of osteosarcoma cells to apoptosis by oncostatin M depends on STAT5 and p53. Chipoy C, Brounais B, Trichet V, Battaglia S, Berreur M, Oliver L, et al. Oncogene. 2007 Oct 11;26(46):6653–64. PubMed Europe PMC Scholia
  11. Box 2 region of the oncostatin M receptor determines specificity for recruitment of Janus kinases and STAT5 activation. Hintzen C, Evers C, Lippok BE, Volkmer R, Heinrich PC, Radtke S, et al. J Biol Chem. 2008 Jul 11;283(28):19465–77. PubMed Europe PMC Scholia
  12. Signal transducer and activator of transcription-3: a molecular hub for signaling pathways in gliomas. Brantley EC, Benveniste EN. Mol Cancer Res. 2008 May;6(5):675–84. PubMed Europe PMC Scholia
  13. A dual role for oncostatin M signaling in the differentiation and death of mammary epithelial cells in vivo. Tiffen PG, Omidvar N, Marquez-Almuina N, Croston D, Watson CJ, Clarkson RWE. Mol Endocrinol. 2008 Dec;22(12):2677–88. PubMed Europe PMC Scholia
  14. CP690,550 inhibits oncostatin M-induced JAK/STAT signaling pathway in rheumatoid synoviocytes. Migita K, Komori A, Torigoshi T, Maeda Y, Izumi Y, Jiuchi Y, et al. Arthritis Res Ther. 2011 May 6;13(3):R72. PubMed Europe PMC Scholia