Oncostatin M signaling pathway (WP3277)

Bos taurus

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 [1]. The major downstream signaling pathways that are activated in OSM signaling are JAK/STAT, Ras/Raf/MAPK and PI3K pathways [2-5]. 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) [1, 6-8]. 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 [1-3, 8]. Alternatively, OSM induced phosphorylation of PTPN11, GRB2, SHC1, Ras/Raf molecules can bring about the activation of ERK1/2 signaling module [1]. 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 [9]. Although OSM also causes induced phosphorylation in MAPK family members (MAPK8/9/14) the functional importance of this is at present not well understood [1, 11]. OSM mediated signaling cascade is negatively regulated by JAK1 inhibition by SOCS3 and STAT3 inhibition by PIAS3 [4-5, 10].OSM also induced the activation of caspase family members (CASP3, CASP7, CASP9) through the JAK2 module and regulates apoptosis [12-14]. In osteosarcoma cells OSM is found to mediate apoptosis through a less understood STAT5B signaling module [14]. 1. O'Hara, K.A., et al., Oncostatin M: an interleukin-6-like cytokine relevant to airway remodelling and the pathogenesis of asthma. Clin Exp Allergy, 2003. 33(8): p. 1026-32. 2. Halfter, H., et al., Activation of Jak-Stat and MAPK2 pathways by oncostatin M leads to growth inhibition of human glioma cells. Mol Cell Biol Res Commun, 1999. 1(2): p. 109-16. 3. 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. 4. Stross, C., et al., Oncostatin M receptor-mediated signal transduction is negatively regulated by SOCS3 through a receptor tyrosine-independent mechanism. J Biol Chem, 2006. 281(13): p. 8458-68. 5. Brantley, E.C. and E.N. Benveniste, Signal transducer and activator of transcription-3: a molecular hub for signaling pathways in gliomas. Mol Cancer Res, 2008. 6(5): p. 675-84. 6. Fritz, D.K., et al., Oncostatin-M up-regulates VCAM-1 and synergizes with IL-4 in eotaxin expression: involvement of STAT6. J Immunol, 2006. 176(7): p. 4352-60. 7. Migita, K., et al., CP690,550 inhibits oncostatin M-induced JAK/STAT signaling pathway in rheumatoid synoviocytes. Arthritis Res Ther, 2011. 13(3): p. R72. 8. 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. 9. Zhang, F., et al., Specific interaction of Egr1 and c/EBPbeta leads to the transcriptional activation of the human low density lipoprotein receptor gene. J Biol Chem, 2003. 278(45): p. 44246-54. 10. Chung, C.D., et al., Specific inhibition of Stat3 signal transduction by PIAS3. Science, 1997. 278(5344): p. 1803-5. 11. 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. 12. Auernhammer, C.J., et al., The oncostatin M receptor/gp130 ligand murine oncostatin M induces apoptosis in adrenocortical Y-1 tumor cells. J Endocrinol, 2004. 180(3): p. 479-86. 13. Tiffen, P.G., et al., A dual role for oncostatin M signaling in the differentiation and death of mammary epithelial cells in vivo. Mol Endocrinol, 2008. 22(12): p. 2677-88. 14. Chipoy, C., et al., Sensitization of osteosarcoma cells to apoptosis by oncostatin M depends on STAT5 and p53. Oncogene, 2007. 26(46): p. 6653-64.

Authors

Martina Summer-Kutmon and Eric Weitz

Activity

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Organisms

Bos taurus

Communities

Annotations

Pathway Ontology

oncostatin M signaling pathway

Participants

Label Type Compact URI Comment
HIF1A GeneProduct ensembl:ENSBTAG00000020935 HomologyConvert: Homo sapiens to Bos taurus: Original ID = En:ENSG00000100644
VEGFA GeneProduct ensembl:ENSBTAG00000047561 HomologyConvert: Homo sapiens to Bos taurus: Original ID = En:ENSG00000112715
MAPK9 Protein ensembl:ENSBTAG00000004709 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5601
MAPK8 Protein ensembl:ENSBTAG00000007876 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5599
MAP2K1 Protein ensembl:ENSBTAG00000033983 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5604
LIFR Protein ensembl:ENSBTAG00000010423 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:3977
JAK2 Protein ensembl:ENSBTAG00000012047 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:3717
PRKCH Protein ensembl:ENSBTAG00000003276 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5583
PRKCE Protein ensembl:ENSBTAG00000020614 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5581
PRKCB Protein ensembl:ENSBTAG00000020921 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5579
PRKCA Protein ensembl:ENSBTAG00000001061 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5578
IL6ST Protein ensembl:ENSBTAG00000017745 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:3572
MAP2K2 Protein ensembl:ENSBTAG00000024450 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5605
STAT3 Protein ensembl:ENSBTAG00000021523 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:6774
STAT1 Protein ensembl:ENSBTAG00000007867 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:6772
JAK1 Protein ensembl:ENSBTAG00000003147 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:3716
MAPK14 Protein ensembl:ENSBTAG00000020783 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:1432
JAK3 Protein ensembl:ENSBTAG00000020904 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:3718
TYK2 Protein ensembl:ENSBTAG00000011698 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:7297
RELA Protein ensembl:ENSBTAG00000013895 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5970
MAPK3 Protein ensembl:ENSBTAG00000016156 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5595
SOCS3 Protein ensembl:ENSBTAG00000008441 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:9021
OSMR Protein ensembl:ENSBTAG00000033107 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:9180
PTPN11 Protein ensembl:ENSBTAG00000002048 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5781
MAPK1 Protein ensembl:ENSBTAG00000010312 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5594
PIAS3 Protein ensembl:ENSBTAG00000021634 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:10401
STAT5B Protein ensembl:ENSBTAG00000010125 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:6777
CASP3 Protein ensembl:ENSBTAG00000015874 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:836
OSM Protein ensembl:ENSBTAG00000016163 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5008
SOS1 Protein ensembl:ENSBTAG00000011643 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:6654
GRB2 Protein ensembl:ENSBTAG00000004736 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:2885
SHC1 Protein ensembl:ENSBTAG00000019838 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:6464
IRS1 Protein ensembl:ENSBTAG00000021308 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:3667
SRC Protein ensembl:ENSBTAG00000008938 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:6714
RAF1 Protein ensembl:ENSBTAG00000045748 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5894
HRAS Protein ensembl:ENSBTAG00000046644 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:3265
PIK3R1 Protein ensembl:ENSBTAG00000010989 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5295
AKT1 Protein ensembl:ENSBTAG00000017636 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:207
FOS Protein ensembl:ENSBTAG00000004322 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:2353
PXN Protein ensembl:ENSBTAG00000018108 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5829
PTK2B Protein ensembl:ENSBTAG00000005958 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:2185
CDK2 Protein ensembl:ENSBTAG00000004021 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:1017
CDKN1B Protein ensembl:ENSBTAG00000018254 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:1027
RPS6 Protein ensembl:ENSBTAG00000014449 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:6194
JUNB Protein ensembl:ENSBTAG00000012046 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:3726
PRKCD Protein ensembl:ENSBTAG00000008719 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5580
MTOR Protein ensembl:ENSBTAG00000015325 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:2475
RICTOR Protein ensembl:ENSBTAG00000006697 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:253260
CREB1 Protein ensembl:ENSBTAG00000005474 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:1385
EGR1 Protein ensembl:ENSBTAG00000010069 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:1958
NFKB1 Protein ensembl:ENSBTAG00000020270 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:4790
BIKBA Protein ensembl:ENSBTAG00000016683 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:4792
CASP7 Protein ensembl:ENSBTAG00000006615 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:840

References