Oncostatin M signaling pathway (WP2374)

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].
last edited

Authors

NetPath, MaintBot, Khanspers, Ddigles, Mkutmon, AlexanderPico, Mechebek maghnaui, and Eweitz

Cited In

Organism

Homo sapiens

Communities

Annotations

Pathway Ontology: oncostatin M signaling pathway

Participants

Label Type Compact Identifier
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
HIF1A GeneProduct ensembl:ENSG00000100644
JAK1 Protein ncbigene:3716
VEGFA GeneProduct ensembl:ENSG00000112715
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
MMP13 Rna ncbigene:4322
TP53 Rna ncbigene:7157
STAT1 Protein ncbigene:6772
STAT5B Protein ncbigene:6777
RICTOR Protein ncbigene:253260
CREB1 Protein ncbigene:1385
CYR61 Rna ncbigene:3491
EGR1 Protein ncbigene:1958
LDLR Rna ncbigene:3949
EGR1 Rna ncbigene:1958
CCL2 Rna ncbigene:6347
MMP1 Rna ncbigene:4312
MMP3 Rna ncbigene:4314
NFKB1 Protein ncbigene:4790
NFKBIA Protein ncbigene:4792
RELA Protein ncbigene:5970
NFKB1 Protein ncbigene:4790
SERPINE1 Rna ncbigene:5054
TIMP3 Rna ncbigene:7078
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

References

  1. Chung CD, Liao J, Liu B, Rao X, Jay P, Berta P, et al. Specific inhibition of Stat3 signal transduction by PIAS3. Science. 1997 Dec 5;278(5344):1803–5. PubMed Europe PMC Scholia
  2. 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 May;1(2):109–16. PubMed Europe PMC Scholia
  3. 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 Sep 15;80(2):198–206. PubMed Europe PMC Scholia
  4. 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 Mar 1;166(5):3491–8. PubMed Europe PMC Scholia
  5. O’Hara KA, Kedda M-A, Thompson PJ, Knight DA. Oncostatin M: an interleukin-6-like cytokine relevant to airway remodelling and the pathogenesis of asthma. Clin Exp Allergy. 2003 Aug;33(8):1026–32. PubMed Europe PMC Scholia
  6. 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 Nov 7;278(45):44246–54. PubMed Europe PMC Scholia
  7. Auernhammer CJ, Dorn F, Vlotides G, Hengge S, Kopp FB, Spoettl G, et al. The oncostatin M receptor/gp130 ligand murine oncostatin M induces apoptosis in adrenocortical Y-1 tumor cells. J Endocrinol. 2004 Mar;180(3):479–86. PubMed Europe PMC Scholia
  8. Stross C, Radtke S, Clahsen T, Gerlach C, Volkmer-Engert R, Schaper F, et al. Oncostatin M receptor-mediated signal transduction is negatively regulated by SOCS3 through a receptor tyrosine-independent mechanism. J Biol Chem. 2006 Mar 31;281(13):8458–68. PubMed Europe PMC Scholia
  9. 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 Apr 1;176(7):4352–60. PubMed Europe PMC Scholia
  10. Chipoy C, Brounais B, Trichet V, Battaglia S, Berreur M, Oliver L, et al. Sensitization of osteosarcoma cells to apoptosis by oncostatin M depends on STAT5 and p53. Oncogene. 2007 Oct 11;26(46):6653–64. PubMed Europe PMC Scholia
  11. Hintzen C, Evers C, Lippok BE, Volkmer R, Heinrich PC, Radtke S, et al. Box 2 region of the oncostatin M receptor determines specificity for recruitment of Janus kinases and STAT5 activation. J Biol Chem. 2008 Jul 11;283(28):19465–77. PubMed Europe PMC Scholia
  12. Brantley EC, Benveniste EN. Signal transducer and activator of transcription-3: a molecular hub for signaling pathways in gliomas. Mol Cancer Res. 2008 May;6(5):675–84. PubMed Europe PMC Scholia
  13. Tiffen PG, Omidvar N, Marquez-Almuina N, Croston D, Watson CJ, Clarkson RWE. A dual role for oncostatin M signaling in the differentiation and death of mammary epithelial cells in vivo. Mol Endocrinol. 2008 Dec;22(12):2677–88. PubMed Europe PMC Scholia
  14. Migita K, Komori A, Torigoshi T, Maeda Y, Izumi Y, Jiuchi Y, et al. CP690,550 inhibits oncostatin M-induced JAK/STAT signaling pathway in rheumatoid synoviocytes. Arthritis Res Ther. 2011 May 6;13(3):R72. PubMed Europe PMC Scholia