Oncostatin M receptor explained

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.[1]

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.[2]

Expression

OSMR is widely expressed across non-haematopoietic, hepatocytes, mesothelial cells, glial cells and epithelial cell types across various organs and mammary glands.[3] OSM receptor is abundantly expressed on endothelial and stromal/fibroblast cells in the lung of mice.[4] =

In vitro expression of OSMR  in fetal hepatocytes is upregulated by OSM stimulation.[5]

OSMR expression has been shown to be induced by parathyroid hormone in osteoblasts and OSM.[6] [7]

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.[8] [9]

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.[10]

Clinical significance

The oncostatin M receptor is associated with primary cutaneous amyloidosis.[11]

OSM signaling via the OSMR is believed to play an important role in bone turnover as Mice lacking the OSMR receptor have osteopetrotic phenotypes.[12] Lack of OSMRβ activity has also been linked to adipose tissue inflammation and insulin resistance preceding obesity.[13]

OSM in-vivo regulation of hematopoiesis, through stimulation of stromal cells & hematopoietic progenitors - megakaryocytic and erythrocytic progenitors, is carried out by the OSMRβ receptor.[14]

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.[15]

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.[16] 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.[16]

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.[17]

OSM-induced biological effects on breast tumor– derived cell lines were specifically mediated through the gp130/OSMRB complex.[18]

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.[19]

OSM and OSMRβ are co-expressed and lead to STAT 3 activation malignant human ovarian epithelial cells.[20]

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.[21]

Notes and References

  1. Mosley B, De Imus C, Friend D, Boiani N, Thoma B, Park LS, Cosman D . 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 . December 1996 . 8999038 . 10.1074/jbc.271.51.32635 . free .
  2. Web site: Entrez Gene: oncostatin M receptor.
  3. West NR, Owens BM, Hegazy AN . The oncostatin M-stromal cell axis in health and disease . Scandinavian Journal of Immunology . 88 . 3 . e12694 . September 2018 . 29926972 . 10.1111/sji.12694 . free .
  4. Machiyama T, So T, Okuyama Y, Kobayashi S, Phung HT, Asao A, Harigae H, Ishii N . TNF receptor associated factor 5 controls oncostatin M-mediated lung inflammation . Biochemical and Biophysical Research Communications . 499 . 3 . 544–550 . May 2018 . 29596835 . 10.1016/j.bbrc.2018.03.186 .
  5. Kamiya A, Kinoshita T, Ito Y, Matsui T, Morikawa Y, Senba E, Nakashima K, Taga T, Yoshida K, Kishimoto T, Miyajima A . Fetal liver development requires a paracrine action of oncostatin M through the gp130 signal transducer . The EMBO Journal . 18 . 8 . 2127–36 . April 1999 . 10205167 . 1171297 . 10.1093/emboj/18.8.2127 .
  6. Walker EC, Poulton IJ, McGregor NE, Ho PW, Allan EH, Quach JM, Martin TJ, Sims NA . 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 . April 2012 . 22190112 . 10.1002/jbmr.1506 . 3475348 . free .
  7. Blanchard F, Wang Y, Kinzie E, Duplomb L, Godard A, Baumann H . 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 . December 2001 . 11602599 . 10.1074/jbc.M107971200 . free .
  8. Hunter CA, Jones SA . IL-6 as a keystone cytokine in health and disease . Nature Immunology . 16 . 5 . 448–57 . May 2015 . 25898198 . 10.1038/ni.3153 . 205369252 .
  9. Heinrich PC, Behrmann I, Haan S, Hermanns HM, Müller-Newen G, Schaper F . Principles of interleukin (IL)-6-type cytokine signalling and its regulation . The Biochemical Journal . 374 . Pt 1 . 1–20 . August 2003 . 12773095 . 1223585 . 10.1042/bj20030407 .
  10. Hermanns HM, Radtke S, Schaper F, Heinrich PC, Behrmann I . 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 . December 2000 . 11016927 . 10.1074/jbc.M005408200 . free .
  11. 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 . Oncostatin M receptor-beta mutations underlie familial primary localized cutaneous amyloidosis . American Journal of Human Genetics . 82 . 1 . 73–80 . January 2008 . 18179886 . 2253984 . 10.1016/j.ajhg.2007.09.002 .
  12. 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 . 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 . February 2010 . 20051625 . 2810087 . 10.1172/jci40568 .
  13. Komori T, Tanaka M, Senba E, Miyajima A, Morikawa Y . 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 . July 2013 . 23760275 . 3724642 . 10.1074/jbc.M113.461905 . free .
  14. Tanaka M, Hirabayashi Y, Sekiguchi T, Inoue T, Katsuki M, Miyajima A . Targeted disruption of oncostatin M receptor results in altered hematopoiesis . Blood . 102 . 9 . 3154–62 . November 2003 . 12855584 . 10.1182/blood-2003-02-0367 . free .
  15. 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 . Therapeutic targeting of the oncostatin M receptor-β prevents inflammatory heart failure . Basic Research in Cardiology . 109 . 1 . 396 . January 2014 . 24292852 . 10.1007/s00395-013-0396-3 . 21889689 .
  16. 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 . Oncostatin M is a major mediator of cardiomyocyte dedifferentiation and remodeling . Cell Stem Cell . 9 . 5 . 420–32 . November 2011 . 22056139 . 10.1016/j.stem.2011.08.013 . free .
  17. Junk DJ, Bryson BL, Smigiel JM, Parameswaran N, Bartel CA, Jackson MW . Oncostatin M promotes cancer cell plasticity through cooperative STAT3-SMAD3 signaling . En . Oncogene . 36 . 28 . 4001–4013 . July 2017 . 28288136 . 5509502 . 10.1038/onc.2017.33 .
  18. Underhill-Day N, Heath JK . Oncostatin M (OSM) cytostasis of breast tumor cells: characterization of an OSM receptor beta-specific kernel . Cancer Research . 66 . 22 . 10891–901 . November 2006 . 17108126 . 10.1158/0008-5472.CAN-06-1766 . free .
  19. Ng G, Winder D, Muralidhar B, Gooding E, Roberts I, Pett M, Mukherjee G, Huang J, Coleman N . 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 . July 2007 . 17516585 . 10.1002/path.2184 . 21134882 .
  20. Savarese TM, Campbell CL, McQuain C, Mitchell K, Guardiani R, Quesenberry PJ, Nelson BE . Coexpression of oncostatin M and its receptors and evidence for STAT3 activation in human ovarian carcinomas . Cytokine . 17 . 6 . 324–34 . March 2002 . 12061840 . 10.1006/cyto.2002.1022 .
  21. 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 . Promoter DNA methylation of oncostatin m receptor-beta as a novel diagnostic and therapeutic marker in colon cancer . PLOS ONE . 4 . 8 . e6555 . August 2009 . 19662090 . 2717211 . 10.1371/journal.pone.0006555 . 2009PLoSO...4.6555K . free .

This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "Oncostatin M receptor".

Except where otherwise indicated, Everything.Explained.Today is © Copyright 2009-2024, A B Cryer, All Rights Reserved. Cookie policy.