Oncostatin M receptor

Last updated
OSMR
Identifiers
Aliases OSMR , OSMRB, PLCA1, IL-31R-beta, IL-31RB, oncostatin M receptor, OSMRbeta
External IDs OMIM: 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 Mb Chr 15: 6.81 – 6.87 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/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]

Contents

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]

Related Research Articles

Interleukin 6 Mammalian protein found in Homo sapiens

Interleukin 6 (IL-6) is an interleukin that acts as both a pro-inflammatory cytokine and an anti-inflammatory myokine. In humans, it is encoded by the IL6 gene.

Interleukin 4

The interleukin 4 is a cytokine that induces differentiation of naive helper T cells to Th2 cells. Upon activation by IL-4, Th2 cells subsequently produce additional IL-4 in a positive feedback loop. IL-4 is produced primarily by mast cells, Th2 cells, eosinophils and basophils. It is closely related and has functions similar to interleukin 13.

Interleukin 3

Interleukin 3 (IL-3) is a protein that in humans is encoded by the IL3 gene localized on chromosome 5q31.1. Sometimes also called colony-stimulating factor, multi-CSF, mast cell growth factor, MULTI-CSF, MCGF; MGC79398, MGC79399: the protein contains 152 amino acids and its molecular weight is 17 kDa. IL-3 is produced as a monomer by activated T cells, monocytes/macrophages and stroma cells. The major function of IL-3 cytokine is to regulate the concentrations of various blood-cell types. It induces proliferation and differentiation in both early pluripotent stem cells and committed progenitors. It also has many more specific effects like the regeneration of platelets and potentially aids in early antibody isotype switching.

Oncostatin M

Oncostatin M, also known as OSM, is a protein that in humans is encoded by the OSM gene.

Caspase 1

Caspase-1/Interleukin-1 converting enzyme (ICE) is an evolutionarily conserved enzyme that proteolytically cleaves other proteins, such as the precursors of the inflammatory cytokines interleukin 1β and interleukin 18 as well as the pyroptosis inducer Gasdermin D, into active mature peptides. It plays a central role in cell immunity as an inflammatory response initiator. Once activated through formation of an inflammasome complex, it initiates a proinflammatory response through the cleavage and thus activation of the two inflammatory cytokines, interleukin 1β (IL-1β) and interleukin 18 (IL-18) as well as pyroptosis, a programmed lytic cell death pathway, through cleavage of Gasdermin D. The two inflammatory cytokines activated by Caspase-1 are excreted from the cell to further induce the inflammatory response in neighboring cells.

Interleukin 11

Interleukin 11 (IL-11) is a protein that in humans is encoded by the IL11 gene.

Interleukin 31

Interleukin-31 (IL-31) is a protein that in humans is encoded by the IL31 gene that resides on chromosome 12. IL-31 is an inflammatory cytokine that helps trigger cell-mediated immunity against pathogens. It has also been identified as a major player in a number of chronic inflammatory diseases, including atopic dermatitis.

Type I cytokine receptors are transmembrane receptors expressed on the surface of cells that recognize and respond to cytokines with four α-helical strands. These receptors are also known under the name hemopoietin receptors, and share a common amino acid motif (WSXWS) in the extracellular portion adjacent to the cell membrane. Members of the type I cytokine receptor family comprise different chains, some of which are involved in ligand/cytokine interaction and others that are involved in signal transduction.

Glycoprotein 130

Glycoprotein 130 is a transmembrane protein which is the founding member of the class of all cytokine receptors. It forms one subunit of the type I cytokine receptor within the IL-6 receptor family. It is often referred to as the common gp130 subunit, and is important for signal transduction following cytokine engagement. As with other type I cytokine receptors, gp130 possesses a WSXWS amino acid motif that ensures correct protein folding and ligand binding. It interacts with Janus kinases to elicit an intracellular signal following receptor interaction with its ligand. Structurally, gp130 is composed of five fibronectin type-III domains and one immunoglobulin-like C2-type (immunoglobulin-like) domain in its extracellular portion.

Leukemia inhibitory factor receptor

LIFR also known as CD118, is a subunit of a receptor for leukemia inhibitory factor.

Tyrosine kinase 2

Non-receptor tyrosine-protein kinase TYK2 is an enzyme that in humans is encoded by the TYK2 gene.

Janus kinase 1

JAK1 is a human tyrosine kinase protein essential for signaling for certain type I and type II cytokines. It interacts with the common gamma chain (γc) of type I cytokine receptors, to elicit signals from the IL-2 receptor family, the IL-4 receptor family, the gp130 receptor family. It is also important for transducing a signal by type I (IFN-α/β) and type II (IFN-γ) interferons, and members of the IL-10 family via type II cytokine receptors. Jak1 plays a critical role in initiating responses to multiple major cytokine receptor families. Loss of Jak1 is lethal in neonatal mice, possibly due to difficulties suckling. Expression of JAK1 in cancer cells enables individual cells to contract, potentially allowing them to escape their tumor and metastasize to other parts of the body.

Interleukin 1 receptor, type I

Interleukin 1 receptor, type I (IL1R1) also known as CD121a, is an interleukin receptor. IL1R1 also denotes its human gene.

IL2RB

Interleukin-2 receptor subunit beta is a protein that in humans is encoded by the IL2RB gene. Also known as CD122; IL15RB; P70-75.

IL31RA

Interleukin-31 receptor A is a protein that in humans is encoded by the IL31RA gene.

IL3RA human gene

Interleukin 3 receptor, alpha (IL3RA), also known as CD123, is a human gene.

The interleukin-5 receptor is a type I cytokine receptor. It is a heterodimer of the interleukin 5 receptor alpha subunit and CSF2RB.

Interleukin-28 receptor is a type II cytokine receptor found largely in epithelial cells. It binds type 3 interferons, interleukin-28 A, Interleukin-28B, interleukin 29 and interferon lambda 4. It consists of an α chain and shares a common β subunit with the interleukin-10 receptor. Binding to the interleukin-28 receptor, which is restricted to select cell types, is important for fighting infection. Binding of the type 3 interferons to the receptor results in activation of the JAK/STAT signaling pathway.

Interleukin-1 family

The Interleukin-1 family is a group of 11 cytokines that plays a central role in the regulation of immune and inflammatory responses to infections or sterile insults.

Interleukin 23

Interleukin-23 is a heterodimeric cytokine composed of an IL12B (IL-12p40) subunit and the IL23A (IL-23p19) subunit. IL-23 is part of IL-12 family of cytokines. A functional receptor for IL-23 has been identified and is composed of IL-12R β1 and IL-23R. Adnectin-2 is binding to IL-23 and compete with IL-23/IL-23R. mRNA of IL-23R is 2,8 kB in length and includes 12 exons. The translated protein contains 629 amino acids, which is a type I penetrating protein includes signal peptide, an N-terminal fibronectin III-like domain and an intracellular part contains 3 potential tyrosine phosphorylation domains. There are 24 variants of splicing of IL-23R in mitogen-activated lymphocytes. IL-23R has some single nucleotide polymorphisms in the domain of binding IL-23 so there can be differences in activation of Th17. There is also variant of IL-23R which has just extracellular part and it´s known as soluble IL-23R. This form can compete with membrane form to bind IL-23 and there can be difference in activation of Th17 immune response and regulation of inflammation and immune function.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000145623 - Ensembl, May 2017
  2. 1 2 3 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. 1 2 "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. 1 2 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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