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Beschreibung

Macrophage-stimulating protein receptor (UniProt: Q04912, also known as EC:2.7.10.1, MSP receptor, CDw136, Protein-tyrosine kinase 8, p185-Ron, RON, CD136) is encoded by the MST1R (also known as PTK8, RON) gene (Gene ID: 4486) in human. CD136/RON, is a single-pass type I membrane glycoprotein of the MET family of receptors, is synthesized with a signal peptide (aa 1-24), which is subsequently cleaved off to generate the mature form that contains an extracellular domain (aa 25-957), a transmembrane domain (aa 958-978), and a cytoplasmic domain (aa 979-1400). It is expressed as a 185-kDa glycosylated pro-form, which is proteolytically processed into a 35 kDa a-chain (aa 25-304) and 150 kDa b-chain (aa 310-1400) that are linked by disulfide bridges. The a-chain is shown to be fully extracellular while the b-chain is composed of an extracellular SEMA domain, three IPT domains, a transmembrane domain and an intracellular tyrosine kinase domain. CD136/RON expression has been reported in colon, skin, lung, and bone marrow. It serves as a receptor tyrosine kinase that transduces signals from the extracellular matrix into the cytoplasm by binding to macrophage stimulating 1 (MST1) ligand and regulates many physiological processes including cell survival, migration, and differentiation. Ligand binding on tyrosine 1238 and 1239 in the kinase domain is shown to induce its autophosphorylation, which leads to further phosphorylation on tyrosine 1353 and 1360 in the C-terminal multi-functional docking site. The activated form interacts with the PI3-kinase subunit PIK3R1, PLCG1, or the adapter GAB1 and the recruitment of these downstream effectors leads to the activation of several signaling cascades including the RAS-ERK, PI3 kinase-AKT, and PLC g -PKC pathways. CD136 signaling is shown to activate the wound healing response by promoting epithelial cell migration, proliferation as well as survival at the wound site. It also plays a role in the innate immune response by regulating the migration and phagocytic activity of macrophages. Mutations in MST1R gene are reported to cause nasopharyngeal carcinoma. Clone 3G4 binds to an epitope on the a-chain and detects a-chain and the pro form of CD136/RON. It is shown to bind strongly to deglycosylated CD136/RON in tunicamycin treated cancer cells. (Ref.: Koh, XY., et al. (2019). Oncogene. 38(48), 7342-7356).