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 activated T lymphocytes, macrophages, monocytes, neutrophils, and 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 lack 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 induces the activation of caspase family members (CASP3, CASP7, CASP9) through the JAK2 module and regulates apoptosis [Auernhammer, Tiffen, Chipoy]. In osteosarcoma cells, OSM mediates apoptosis through a less understood STAT5B signaling module [Chipoy].
Authors
NetPath , Kristina Hanspers , Daniela Digles , Martina Summer-Kutmon , Alex Pico , Mechebek Maghnaui , Eric Weitz , and Egon WillighagenActivity
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Cited In
- Long Term Culture of the A549 Cancer Cell Line Promotes Multilamellar Body Formation and Differentiation towards an Alveolar Type II Pneumocyte Phenotype (2016).
- Signaling network of Oncostatin M pathway (2012).
- In silico transcriptional analysis of asymptomatic and severe COVID-19 patients reveals the susceptibility of severe patients to other comorbidities and non-viral pathological conditions (2023).
- A Practical Strategy for Exploring the Pharmacological Mechanism of Luteolin Against COVID-19/Asthma Comorbidity: Findings of System Pharmacology and Bioinformatics Analysis (2024).
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Organisms
Homo sapiensCommunities
Annotations
Cell Type Ontology
mammary gland epithelial cell osteoblast astrocyte aortic smooth muscle cell cortical cell of adrenal gland luminal epithelial cell of mammary glandPathway Ontology
oncostatin M signaling pathwayDisease Ontology
osteosarcoma lung carcinoma| 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 | |
| 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 | |
| PIAS3 | Protein | ncbigene:10401 | |
| 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 | |
| RAF1 | Protein | ncbigene:5894 | |
| HRAS | Protein | ncbigene:3265 | |
| PIK3R1 | Protein | ncbigene:5295 | |
| AKT1 | Protein | ncbigene:207 | |
| 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 | |
| PRKCD | Protein | ncbigene:5580 | |
| MTOR | Protein | ncbigene:2475 | |
| RICTOR | Protein | ncbigene:253260 | |
| CREB1 | Protein | ncbigene:1385 | |
| EGR1 | Protein | ncbigene:1958 | |
| NFKB1 | Protein | ncbigene:4790 | |
| NFKBIA | Protein | ncbigene:4792 | |
| CASP7 | Protein | ncbigene:840 | |
| CASP9 | Protein | ncbigene:840 |
References
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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