Oncostatin M receptor

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OSMR
Identifiers
AliasesOSMR, OSMRB, PLCA1, IL-31R-beta, IL-31RB, oncostatin M receptor, OSMRbeta
External IDsOMIM: 601743 MGI: 1330819 HomoloGene: 2972 GeneCards: OSMR
Gene location (Human)
Chromosome 5 (human)
Chr.Chromosome 5 (human)[1]
Chromosome 5 (human)
Genomic location for OSMR
Genomic location for OSMR
Band5p13.1Start38,845,858 bp[1]
End38,945,596 bp[1]
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_011019
NM_001310469

RefSeq (protein)

NP_001297398
NP_035149

Location (UCSC)Chr 5: 38.85 – 38.95 MbChr 15: 6.81 – 6.87 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

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 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[edit]

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[edit]

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[edit]

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[edit]

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[edit]

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[edit]

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000145623 - Ensembl, May 2017
  2. ^ a b c 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. ^ a b "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.
  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.
  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.
  20. ^ a b 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.
  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. doi:10.1371/journal.pone.0006555. PMC 2717211. PMID 19662090.

External links[edit]

This article incorporates text from the United States National Library of Medicine, which is in the public domain.