Oncostatin M Signaling Pathway (Homo sapiens)

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JAK2Y1007PRKCHPPRKCEPPRKCBPPRKCAPSTAT1IL6STMAPK9MAP2K2S226STAT3Y705STAT1Y701ApoptosisOncostatin M Signaling PathwayJAK1Y1022MAPK14Y180MAPK8T183JAK3Y980TYK2Y1054RELAPLIFRPMAP2K1MAPK3Y204SOCS3OSMRY861PTPN11Y542MAPK1STAT1Y701PIAS3STAT5BSTAT5BY699CASP3PARP1OSMIL6STPSOS1GRB2SHC1PIRS1PSRCY419STAT3S727Y705RAF1S338HRASGTPPIK3R1AKT1OSMSTAT3STAT1FOSPXNPTK2BPSOCS3CDK2CDKN1BCEBPBPRPS6S235JUNSTAT3STAT3PRKCDPMTORMMP13ADAMTS4TIMP1TP53CCND1STAT1STAT5BSTAT5BRICTORCREB1S133CRY61EGR1LDLREGR1MAPK3MAPK1CCL2TIMP3MMP1MMP3CISHNFKB1NFKBIARELANFKB1SERPINE1TIMP3CYNUCYNUCYNUCYNUCYNUCYNUCYNUIncrease in proliferationVascular pathologiesRegulates blood cholesterolIncrease in proliferationY580S727Y1023Y1008S222S218Y182Y185T183T308S473S236Y1055Y202Y185Y187Y759T782Y701Y705Y699Y699Y705Y701Y187Y202Y185Y204Y701Y705


Description

As a member of the Interleukine (IL-6) cytotkine superfamily, Oncostatin M (OSM) besides, contributing to the normal physiology of repair, remodeling and hematopoiesis, also plays an important role in pathological conditions such as oncogenesis and inflammation (add ref). The activation of OSM receptors (LIFR and OSMR beta) by OSM, causes the formation of heterodimeric complex of LIFR-gp130 or OSMR-gp130 .

OSM mediated stimulation of its receptors, causes the activation of downstream signaling cascades. JAK/STAT, Ras/Raf/MAPK and PI 3-kinase through phosphorylation . On phosphorylation the STATs undergo homo- or hetero-dimerization, followed by their nuclear translocation and subsequent regulation of target gene expression . The dual effects of OSM, is mediated through the variation in phosphorylation of residues at selected sites, in different cell types or conditions. The OSM stimulation of JAK/STAT/PI 3 K leads to the increased expression of SOCS3 mRNA . The increased SOCS3 expression in turn effects the inactivation of JAK1, upon OSM stimulation.

1. Auguste, P., et al., Signaling of type II oncostatin M receptor. J Biol Chem, 1997. 272(25): p. 15760-4. 2. !!! INVALID CITATION !!! 3. Blanchard, F., et al., Oncostatin M regulates the synthesis and turnover of gp130, leukemia inhibitory factor receptor alpha, and oncostatin M receptor beta by distinct mechanisms. J Biol Chem, 2001. 276(50): p. 47038-45. 4. 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. 5. Lin, S.K., et al., MEK/ERK and signal transducer and activator of transcription signaling pathways modulate oncostatin M-stimulated CCL2 expression in human osteoblasts through a common transcription factor. Arthritis Rheum, 2004. 50(3): p. 785-93. 6. 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. 7. 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. 8. Ihn, H. and K. Tamaki, Oncostatin M stimulates the growth of dermal fibroblasts via a mitogen-activated protein kinase-dependent pathway. J Immunol, 2000. 165(4): p. 2149-55. 9. Mahboubi, K., et al., Desensitization of signaling by oncostatin M in human vascular cells involves cytoplasmic Tyr residue 759 in gp130 but is not mediated by either Src homology 2 domain-containing tyrosine phosphatase 2 or suppressor of cytokine signaling 3. J Biol Chem, 2003. 278(27): p. 25014-23.

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54190view13:06, 23 November 2012NetPathDeleted pathway: wrong map
53439view05:20, 7 November 2012NetPathModified description
53438view05:20, 7 November 2012NetPathModified description
53437view05:19, 7 November 2012NetPathModified description
53436view05:18, 7 November 2012NetPathModified description
53435view05:17, 7 November 2012NetPathModified description
53434view05:09, 7 November 2012NetPathNew pathway

External references

DataNodes

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NameTypeDatabase referenceComment
ADAMTS4Rna9507 (Entrez Gene)
AKT1Protein207 (Entrez Gene)
CASP3Protein836 (Entrez Gene)
CCL2Rna6347 (Entrez Gene)
CCND1Rna595 (Entrez Gene)
CDK2Protein1017 (Entrez Gene)
CDKN1BProtein1027 (Entrez Gene)
CEBPBProtein1051 (Entrez Gene)
CISHRna1154 (Entrez Gene)
CREB1Protein1385 (Entrez Gene)
CRY61Rna3491 (Entrez Gene)
EGR1Rna1958 (Entrez Gene)
FOSProtein2353 (Entrez Gene)
GRB2Protein2885 (Entrez Gene)
HRASProtein3265 (Entrez Gene)
IL6STProtein3572 (Entrez Gene)
IRS1Protein3667 (Entrez Gene)
JAK1Protein3716 (Entrez Gene)
JAK2Protein3717 (Entrez Gene)
JAK3Protein3718 (Entrez Gene)
JUNProtein3725 (Entrez Gene)
LDLRRna3949 (Entrez Gene)
LIFRProtein3977 (Entrez Gene)
MAP2K1Protein5604 (Entrez Gene)
MAP2K2Protein5605 (Entrez Gene)
MAPK14Protein1432 (Entrez Gene)
MAPK1Protein5594 (Entrez Gene)
MAPK3Protein5595 (Entrez Gene)
MAPK8Protein5599 (Entrez Gene)
MAPK9Protein5601 (Entrez Gene)
MMP13Rna4322 (Entrez Gene)
MMP1Rna4312 (Entrez Gene)
MMP3Rna4314 (Entrez Gene)
MTORProtein2475 (Entrez Gene)
NFKB1Protein4790 (Entrez Gene)
NFKBIAProtein4792 (Entrez Gene)
OSMProtein5008 (Entrez Gene)
OSMRProtein9180 (Entrez Gene)
PARP1Protein142 (Entrez Gene)
PIAS3Protein10401 (Entrez Gene)
PIK3R1Protein5295 (Entrez Gene)
PRKCAProtein5578 (Entrez Gene)
PRKCBProtein5579 (Entrez Gene)
PRKCDProtein5580 (Entrez Gene)
PRKCEProtein5581 (Entrez Gene)
PRKCHProtein5583 (Entrez Gene)
PTK2BProtein2185 (Entrez Gene)
PTPN11Protein5781 (Entrez Gene)
PXNProtein5829 (Entrez Gene)
RAF1Protein5894 (Entrez Gene)
RELAProtein5970 (Entrez Gene)
RICTORProtein253260 (Entrez Gene)
RPS6Protein6194 (Entrez Gene)
SERPINE1Rna5054 (Entrez Gene)
SHC1Protein6464 (Entrez Gene)
SOCS3Rna9021 (Entrez Gene)
SOS1Protein6654 (Entrez Gene)
SRCProtein6714 (Entrez Gene)
STAT1Protein6772 (Entrez Gene)
STAT3Protein6774 (Entrez Gene)
STAT5BProtein6777 (Entrez Gene)
TIMP1Rna7076 (Entrez Gene)
TIMP3Rna7078 (Entrez Gene)
TP53Rna7157 (Entrez Gene)
TYK2Protein7297 (Entrez Gene)

Annotated Interactions

No annotated interactions

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