Oncostatin M Signaling Pathway (Bos taurus)

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JUNDKRASGTPMAPK9MAPK8Y185T183MAP2K1S218LIFRPJAK2Y1007Y1007PRKCHPPRKCEPPRKCBPPRKCAPIL6STY759MAP2K2S222S226STAT3Y705STAT1Y701IL6STY782DissociationSensitization of osteosarcoma cellsto apoptosisAdrenocortical Y-1 cells Mammary epithelial cells In astrocytes,adipose tissues,VSMCs, and inlung carcinomaMEKdependentOncostatin M Signaling PathwayApoptosis in VEGFAJAK1HIF1AY1022Y1023MAPK14Y182Y180JAK3Y980TYK2Y1054Y1055RELAPMAPK3Y204Y202SOCS3OSMRY861PTPN11Y580Y542MAPK1Y185Y187STAT1Y701PIAS3STAT5BSTAT5BY699CASP3OSMSOS1GRB2SHC1PIRS1PSRCY419STAT3Y705S727RAF1S338HRASGTPPIK3R1AKT1S473T308OSMSTAT3Y705STAT1Y701FOSPXNPTK2BPCDK2CDKN1BCEBPBPRPS6S236S235JUNBPSTAT3PRKCDPMTORMMP13TP53STAT1STAT5BRICTORCREB1S133CYR61EGR1LDLREGR1CCL2MMP1MMP3NFKB1BIKBAPUbRELANFKB1SERPINE1TIMP3CYNUCYNUCYNUCYNUCYNUCYNUCYNUIncrease in proliferationRegulation ofblood cholesterolIncrease in proliferationRegulation of osteoblastdifferentiationand activityCytoskeletonreorganizationSTAT5BY699STAT3Y705STAT1Y701MAPK3Y202Y204MAPK1Y187Y185Plaqueangiogenesis and destabilization incoronary arteryand arotic smoothmuscle cellsIn humanosteoblasts andU2OS cellsCartilagedegradationGrowthinhibitionin MCF-7cellsCASP7ProteinReceptorProteinProteinmRNALigandInduced activationEnzyme complexInhibitionTransportPositive regulation of gene expressionLeads to through unknown mechanismNegative regulation of gene expressionTranslocation Induced catalysisProtein-protein interaction (PPI)LEGENDPhosphorylationNucleusCytoplasmCYNUActivationCASP7Dissociation of PPI


Description

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.

Comments

HomologyConvert 
This pathway was inferred from Homo sapiens pathway WP2374(73668) with a 96.0% conversion rate.

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History

CompareRevisionActionTimeUserComment
80930view15:31, 30 June 2015MkutmonNew pathway

External references

DataNodes

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NameTypeDatabase referenceComment
AKT1ProteinENSBTAG00000017636 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:207
BIKBAProteinENSBTAG00000016683 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:4792
CASP3ProteinENSBTAG00000015874 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:836
CASP7ProteinENSBTAG00000006615 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:840
CCL2RnaENSBTAG00000037811 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:6347
CDK2ProteinENSBTAG00000004021 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:1017
CDKN1BProteinENSBTAG00000018254 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:1027
CEBPBProtein
CREB1ProteinENSBTAG00000005474 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:1385
CYR61RnaENSBTAG00000009844 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:3491
EGR1RnaENSBTAG00000010069 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:1958
FOSProteinENSBTAG00000004322 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:2353
GRB2ProteinENSBTAG00000004736 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:2885
HIF1AGeneProductENSBTAG00000020935 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = En:ENSG00000100644
HRASProteinENSBTAG00000046644 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:3265
IL6STProteinENSBTAG00000017745 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:3572
IRS1ProteinENSBTAG00000021308 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:3667
JAK1ProteinENSBTAG00000003147 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:3716
JAK2ProteinENSBTAG00000012047 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:3717
JAK3ProteinENSBTAG00000020904 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:3718
JUNBProteinENSBTAG00000012046 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:3726
JUNDProtein
KRASProtein
LDLRRnaENSBTAG00000012314 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:3949
LIFRProteinENSBTAG00000010423 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:3977
MAP2K1ProteinENSBTAG00000033983 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5604
MAP2K2ProteinENSBTAG00000024450 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5605
MAPK14ProteinENSBTAG00000020783 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:1432
MAPK1ProteinENSBTAG00000010312 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5594
MAPK3ProteinENSBTAG00000016156 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5595
MAPK8ProteinENSBTAG00000007876 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5599
MAPK9ProteinENSBTAG00000004709 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5601
MMP13RnaENSBTAG00000015059 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:4322
MMP1RnaENSBTAG00000048029 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:4312
MMP3RnaENSBTAG00000037768 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:4314
MTORProteinENSBTAG00000015325 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:2475
NFKB1ProteinENSBTAG00000020270 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:4790
OSMProteinENSBTAG00000016163 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5008
OSMRProteinENSBTAG00000033107 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:9180
PIAS3ProteinENSBTAG00000021634 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:10401
PIK3R1ProteinENSBTAG00000010989 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5295
PRKCAProteinENSBTAG00000001061 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5578
PRKCBProteinENSBTAG00000020921 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5579
PRKCDProteinENSBTAG00000008719 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5580
PRKCEProteinENSBTAG00000020614 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5581
PRKCHProteinENSBTAG00000003276 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5583
PTK2BProteinENSBTAG00000005958 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:2185
PTPN11ProteinENSBTAG00000002048 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5781
PXNProteinENSBTAG00000018108 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5829
RAF1ProteinENSBTAG00000045748 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5894
RELAProteinENSBTAG00000013895 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5970
RICTORProteinENSBTAG00000006697 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:253260
RPS6ProteinENSBTAG00000014449 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:6194
SERPINE1RnaENSBTAG00000014465 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5054
SHC1ProteinENSBTAG00000019838 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:6464
SOCS3ProteinENSBTAG00000008441 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:9021
SOS1ProteinENSBTAG00000011643 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:6654
SRCProteinENSBTAG00000008938 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:6714
STAT1ProteinENSBTAG00000007867 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:6772
STAT3ProteinENSBTAG00000021523 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:6774
STAT5BProteinENSBTAG00000010125 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:6777
TIMP3RnaENSBTAG00000020638 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:7078
TP53RnaENSBTAG00000001069 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:7157
TYK2ProteinENSBTAG00000011698 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:7297
VEGFAGeneProductENSBTAG00000047561 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = En:ENSG00000112715

Annotated Interactions

No annotated interactions
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