Oncostatin-M specific receptor subunit beta also known as the Oncostatin M receptor (OSMR) , is one of the receptor proteins for

oncostatin M Oncostatin M, also known as OSM, is a protein that in humans is encoded by the ''OSM'' gene. OSM is a pleiotropic cytokine that belongs to the interleukin 6 group of cytokines. Of these cytokines it most closely resembles leukemia inhibitory fact ...

, that in humans is encoded by the ''OSMR''

gene In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...

. OSMR is a member of the

type I cytokine receptor 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 c ...

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

and interleukin 31 induced signaling events.

Expression

OSMR is widely expressed across non-haematopoietic, hepatocytes, mesothelial cells, glial cells and epithelial cell types across various organs and mammary glands. OSM receptor is abundantly expressed on endothelial and stromal/fibroblast cells in the lung of mice.= In vitro expression of OSMR in fetal hepatocytes is upregulated by OSM stimulation. OSMR expression has been shown to be induced by parathyroid hormone in osteoblasts and OSM.

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 Glycoprotein 130 (also known as gp130, IL6ST, IL6R-beta or CD130) 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 famil ...

. Activation of the OSMR-gp130 complex by OSM triggers Janus Kinase 1 ( JAK1) and

Jak2 Janus kinase 2 (commonly called JAK2) is a non-receptor tyrosine kinase. It is a member of the Janus kinase family and has been implicated in signaling by members of the type II cytokine receptor family (e.g. interferon receptors), the GM-CSF rece ...

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 Phosphoinositide 3-kinases (PI3Ks), also called phosphatidylinositol 3-kinases, are a family of enzymes involved in cellular functions such as cell growth, proliferation, differentiation, motility, survival and intracellular trafficking, which i ...

cascade and

STAT3 Signal transducer and activator of transcription 3 (STAT3) is a transcription factor which in humans is encoded by the ''STAT3'' gene. It is a member of the STAT protein family. Function STAT3 is a member of the STAT protein family. In respons ...

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

JNK c-Jun N-terminal kinases (JNKs), were originally identified as kinases that bind and phosphorylate c-Jun on Ser-63 and Ser-73 within its transcriptional activation domain. They belong to the mitogen-activated protein kinase family, and ar ...

activation.

Clinical significance

The oncostatin M receptor is associated with primary cutaneous amyloidosis. OSM signaling via the OSMR is believed to play an important role in bone turnover as Mice lacking the OSMR receptor have osteopetrotic phenotypes. Lack of OSMRβ activity has also been linked to adipose tissue inflammation and insulin resistance preceding obesity. OSM in-vivo regulation of hematopoiesis, through stimulation of stromal cells & hematopoietic progenitors - megakaryocytic and erythrocytic progenitors, is carried out by the OSMRβ receptor.

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. 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. 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.

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. OSM-induced biological effects on breast tumor– derived cell lines were specifically mediated through the gp130/OSMRB complex. 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. OSM and OSMRβ are co-expressed and lead to STAT 3 activation malignant human ovarian epithelial cells. ''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.

References

External links

* {{Cytokine receptor modulators Type I cytokine receptors