Oncostatin M receptor

Oncostatin-M specific receptor subunit beta also known as the Oncostatin M receptor (OSMR) , is one of the receptor proteins for oncostatin M, that in humans is encoded by the OSMR gene.[5][6]

OSMR
Identifiers
AliasesOSMR, OSMRB, PLCA1, IL-31R-beta, IL-31RB, oncostatin M receptor, OSMRbeta
External IDsOMIM: 601743 MGI: 1330819 HomoloGene: 2972 GeneCards: OSMR
Orthologs
SpeciesHumanMouse
Entrez

9180

18414

Ensembl

ENSG00000145623

ENSMUSG00000022146

UniProt

Q99650

O70458

RefSeq (mRNA)

NM_011019
NM_001310469

RefSeq (protein)

NP_001297398
NP_035149

Location (UCSC)Chr 5: 38.85 – 38.95 MbChr 15: 6.84 – 6.9 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

OSMR is a member of the type I cytokine receptor family. This protein heterodimerizes with interleukin 6 signal transducer to form the type II oncostatin M receptor and with interleukin 31 receptor A to form the interleukin 31 receptor, and thus transduces oncostatin M and interleukin 31 induced signaling events.[5]

Expression

OSMR is widely expressed across non-haematopoietic, hepatocytes, mesothelial cells, glial cells and epithelial cell types across various organs and mammary glands.[7] OSM receptor is abundantly expressed on endothelial and stromal/fibroblast cells in the lung of mice.[8]=

In vitro expression of OSMR  in fetal hepatocytes is upregulated by OSM stimulation.[9]

OSMR expression has been shown to be induced by parathyroid hormone in osteoblasts and OSM.[10][11]

Signaling

Intracellular cell signalling occurs as a consequence of extracellular binding of the ligand OSM to OSMR complexes, formed from dimerization with receptor subunits such as gp130. Activation of the OSMR-gp130 complex by OSM triggers Janus Kinase 1 (JAK1) and Jak2 cross phosphorylation of tyrosine residues on the intracellular receptor domain. Downstream signaling activation of the OSMR-gp130 complex  along the JAK1 pathway leads to IL-6 signalling which is linked with activation of the MAPK cascade, PI3K cascade and STAT3 activation.[12][13]

OSM induced recruitment of SHC to the OSMRβ sub-unit has been shown to enhance Ras/Raf/MAPK signaling and lead p38 and JNK activation.[14]

Clinical significance

The oncostatin M receptor is associated with primary cutaneous amyloidosis.[15]

OSM signaling via the OSMR is believed to play an important role in bone turnover as Mice lacking the OSMR receptor have osteopetrotic phenotypes.[16] Lack of OSMRβ activity has also been linked to adipose tissue inflammation and insulin resistance preceding obesity.[17]

OSM in-vivo regulation of hematopoiesis, through stimulation of stromal cells & hematopoietic progenitors - megakaryocytic and erythrocytic progenitors, is carried out by the OSMRβ receptor.[18]

Heart Disease

Inhibition of the OSMRβ extracellular subunit has been shown has been shown to prevent OSM-mediated down-regulation of myoglobin in cardiomyocytes and related apoptosis of cardiomyocytes in inflammatory heart failure.[19]

OSMRβ is not only overexpressed in patients with chronic dilated cardiomyopathy but has been shown to control dedifferentiation and loss of sarcomeric structures in myocardial infarction and dilated cardio myopathy.[20] OSM and OSMRβ mediated dedifferentiation  has been shown to increase chances of survival after acute myocardial damage but poor survival rates and compromised pump functions in chronic disease states.[20]

Cancer

OSMR activates STAT3 and transforming growth factor β (TGF-β) effector SMAD3 to regulate expression of genes responsible for inducing a mesenchymal/CSC phenotype.[21]

OSM-induced biological effects on breast tumor– derived cell lines were specifically mediated through the gp130/OSMRB complex.[22]

the OSM receptor (OSMR) is overexpressed in cervical squamous cell carcinomas and, independent of tumor stage, is associated with adverse clinical outcomes and higher relative risk of death.[23]

OSM and OSMRβ are co-expressed and lead to STAT 3 activation malignant human ovarian epithelial cells.[24]

The OSMR β  promoter gene is highly methylated in primary Colorectal Cancer tissues and  fecal DNA, it is a highly specific diagnostic biomarker of Colorectal Cancer.[25]

References
  1. GRCh38: Ensembl release 89: ENSG00000145623 - Ensembl, May 2017
  2. GRCm38: Ensembl release 89: ENSMUSG00000022146 - Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. "Entrez Gene: oncostatin M receptor".
  6. Mosley B, De Imus C, Friend D, Boiani N, Thoma B, Park LS, Cosman D (December 1996). "Dual oncostatin M (OSM) receptors. Cloning and characterization of an alternative signaling subunit conferring OSM-specific receptor activation". The Journal of Biological Chemistry. 271 (51): 32635–43. doi:10.1074/jbc.271.51.32635. PMID 8999038.
  7. West NR, Owens BM, Hegazy AN (September 2018). "The oncostatin M-stromal cell axis in health and disease". Scandinavian Journal of Immunology. 88 (3): e12694. doi:10.1111/sji.12694. PMID 29926972.
  8. Machiyama T, So T, Okuyama Y, Kobayashi S, Phung HT, Asao A, Harigae H, Ishii N (May 2018). "TNF receptor associated factor 5 controls oncostatin M-mediated lung inflammation". Biochemical and Biophysical Research Communications. 499 (3): 544–550. doi:10.1016/j.bbrc.2018.03.186. PMID 29596835.
  9. Kamiya A, Kinoshita T, Ito Y, Matsui T, Morikawa Y, Senba E, Nakashima K, Taga T, Yoshida K, Kishimoto T, Miyajima A (April 1999). "Fetal liver development requires a paracrine action of oncostatin M through the gp130 signal transducer". The EMBO Journal. 18 (8): 2127–36. doi:10.1093/emboj/18.8.2127. PMC 1171297. PMID 10205167.
  10. Walker EC, Poulton IJ, McGregor NE, Ho PW, Allan EH, Quach JM, Martin TJ, Sims NA (April 2012). "Sustained RANKL response to parathyroid hormone in oncostatin M receptor-deficient osteoblasts converts anabolic treatment to a catabolic effect in vivo". Journal of Bone and Mineral Research. 27 (4): 902–12. doi:10.1002/jbmr.1506. PMID 22190112. S2CID 3475348.
  11. Blanchard F, Wang Y, Kinzie E, Duplomb L, Godard A, Baumann H (December 2001). "Oncostatin M regulates the synthesis and turnover of gp130, leukemia inhibitory factor receptor alpha, and oncostatin M receptor beta by distinct mechanisms". The Journal of Biological Chemistry. 276 (50): 47038–45. doi:10.1074/jbc.M107971200. PMID 11602599.
  12. Hunter CA, Jones SA (May 2015). "IL-6 as a keystone cytokine in health and disease". Nature Immunology. 16 (5): 448–57. doi:10.1038/ni.3153. PMID 25898198. S2CID 205369252.
  13. Heinrich PC, Behrmann I, Haan S, Hermanns HM, Müller-Newen G, Schaper F (August 2003). "Principles of interleukin (IL)-6-type cytokine signalling and its regulation". The Biochemical Journal. 374 (Pt 1): 1–20. doi:10.1042/bj20030407. PMC 1223585. PMID 12773095.
  14. Hermanns HM, Radtke S, Schaper F, Heinrich PC, Behrmann I (December 2000). "Non-redundant signal transduction of interleukin-6-type cytokines. The adapter protein Shc is specifically recruited to the oncostatin M receptor". The Journal of Biological Chemistry. 275 (52): 40742–8. doi:10.1074/jbc.M005408200. PMID 11016927.
  15. Arita K, South AP, Hans-Filho G, Sakuma TH, Lai-Cheong J, Clements S, Odashiro M, Odashiro DN, Hans-Neto G, Hans NR, Holder MV, Bhogal BS, Hartshorne ST, Akiyama M, Shimizu H, McGrath JA (January 2008). "Oncostatin M receptor-beta mutations underlie familial primary localized cutaneous amyloidosis". American Journal of Human Genetics. 82 (1): 73–80. doi:10.1016/j.ajhg.2007.09.002. PMC 2253984. PMID 18179886.
  16. Walker EC, McGregor NE, Poulton IJ, Solano M, Pompolo S, Fernandes TJ, Constable MJ, Nicholson GC, Zhang JG, Nicola NA, Gillespie MT, Martin TJ, Sims NA (February 2010). "Oncostatin M promotes bone formation independently of resorption when signaling through leukemia inhibitory factor receptor in mice". The Journal of Clinical Investigation. 120 (2): 582–92. doi:10.1172/jci40568. PMC 2810087. PMID 20051625.
  17. Komori T, Tanaka M, Senba E, Miyajima A, Morikawa Y (July 2013). "Lack of oncostatin M receptor β leads to adipose tissue inflammation and insulin resistance by switching macrophage phenotype". The Journal of Biological Chemistry. 288 (30): 21861–75. doi:10.1074/jbc.M113.461905. PMC 3724642. PMID 23760275.
  18. Tanaka M, Hirabayashi Y, Sekiguchi T, Inoue T, Katsuki M, Miyajima A (November 2003). "Targeted disruption of oncostatin M receptor results in altered hematopoiesis". Blood. 102 (9): 3154–62. doi:10.1182/blood-2003-02-0367. PMID 12855584.
  19. Pöling J, Gajawada P, Richter M, Lörchner H, Polyakova V, Kostin S, Shin J, Boettger T, Walther T, Rees W, Wietelmann A, Warnecke H, Kubin T, Braun T (January 2014). "Therapeutic targeting of the oncostatin M receptor-β prevents inflammatory heart failure". Basic Research in Cardiology. 109 (1): 396. doi:10.1007/s00395-013-0396-3. PMID 24292852. S2CID 21889689.
  20. Kubin T, Pöling J, Kostin S, Gajawada P, Hein S, Rees W, Wietelmann A, Tanaka M, Lörchner H, Schimanski S, Szibor M, Warnecke H, Braun T (November 2011). "Oncostatin M is a major mediator of cardiomyocyte dedifferentiation and remodeling". Cell Stem Cell. 9 (5): 420–32. doi:10.1016/j.stem.2011.08.013. PMID 22056139.
  21. Junk DJ, Bryson BL, Smigiel JM, Parameswaran N, Bartel CA, Jackson MW (July 2017). "Oncostatin M promotes cancer cell plasticity through cooperative STAT3-SMAD3 signaling". Oncogene. 36 (28): 4001–4013. doi:10.1038/onc.2017.33. PMC 5509502. PMID 28288136.
  22. Underhill-Day N, Heath JK (November 2006). "Oncostatin M (OSM) cytostasis of breast tumor cells: characterization of an OSM receptor beta-specific kernel". Cancer Research. 66 (22): 10891–901. doi:10.1158/0008-5472.CAN-06-1766. PMID 17108126.
  23. Ng G, Winder D, Muralidhar B, Gooding E, Roberts I, Pett M, Mukherjee G, Huang J, Coleman N (July 2007). "Gain and overexpression of the oncostatin M receptor occur frequently in cervical squamous cell carcinoma and are associated with adverse clinical outcome". The Journal of Pathology. 212 (3): 325–34. doi:10.1002/path.2184. PMID 17516585. S2CID 21134882.
  24. Savarese TM, Campbell CL, McQuain C, Mitchell K, Guardiani R, Quesenberry PJ, Nelson BE (March 2002). "Coexpression of oncostatin M and its receptors and evidence for STAT3 activation in human ovarian carcinomas". Cytokine. 17 (6): 324–34. doi:10.1006/cyto.2002.1022. PMID 12061840.
  25. Kim MS, Louwagie J, Carvalho B, Terhaar Sive Droste JS, Park HL, Chae YK, Yamashita K, Liu J, Ostrow KL, Ling S, Guerrero-Preston R, Demokan S, Yalniz Z, Dalay N, Meijer GA, Van Criekinge W, Sidransky D (August 2009). "Promoter DNA methylation of oncostatin m receptor-beta as a novel diagnostic and therapeutic marker in colon cancer". PLOS ONE. 4 (8): e6555. Bibcode:2009PLoSO...4.6555K. doi:10.1371/journal.pone.0006555. PMC 2717211. PMID 19662090.

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