background:
MST1R/Ron, a HGF Receptor/MET-type protein kinase, mediates the biological activities of macrophage-stimulating protein (MSP), a multifunctional cytokine that regulates cell adhesion, motility, growth, and survival. The protein is a membrane-spanning, disulfide-linked heterodimer, which results from cleavage of a glycosylated precursor into 35-kD (alpha) and 150-kD (beta) subunits. Ligand binding results in tyrosine phosphorylation of the beta chain. In knockout studies, MST1R/RON (-/-) mice failed to survive past the periimplantation period. The MST1R/RON gene has been mapped to 3p21, a region of frequent deletion or mutation in small cell lung and renal carcinoma, and has been implicated in the progression of several epithelial cancers. Ron expression has been documented in many normal human tissues. ESTs have been isolated from several tissue libraries, including normal colon, mouth, prostate, and testis and cancerous colon, prostate, stomach, and uterus.
Function:
Receptor tyrosine kinase that transduces signals from the extracellular matrix into the cytoplasm by binding to MST1 ligand. Regulates many physiological processes including cell survival, migration and differentiation. Ligand binding at the cell surface induces autophosphorylation of RON on its intracellular domain that provides docking sites for downstream signaling molecules. Following activation by ligand, interacts with the PI3-kinase subunit PIK3R1, PLCG1 or the adapter GAB1. Recruitment of these downstream effectors by RON leads to the activation of several signaling cascades including the RAS-ERK, PI3 kinase-AKT, or PLCgamma-PKC. RON signaling activates the wound healing response by promoting epithelial cell migration, proliferation as well as survival at the wound site. Plays also a role in the innate immune response by regulating the migration and phagocytic activity of macrophages. Alternatively, RON can also promote signals such as cell migration and proliferation in response to growth factors other than MST1 ligand.
Subunit:
Heterodimer of an alpha chain and a beta chain which are disulfide linked. Binds PLXNB1. Associates with and is negatively regulated by HYAL2. Interacts when phosphorylated with downstream effectors including PIK3R1, PCLG1, GRB2 and GAB1. Interacts with integrin beta1/ITGB1 in a ligand-independent fashion.
Subcellular Location:
Membrane; Single-pass type I membrane protein.
Tissue Specificity:
Expressed in colon, skin, lung and bone marrow.
Post-translational modifications:
Proteolytic processing yields the two subunits.
Autophosphorylated in response to ligand binding on Tyr-1238 and Tyr-1239 in the kinase domain leading to further phosphorylation of Tyr-1353 and Tyr-172 in the SLCterminal multifunctional docking site.
Ubiquitinated. Ubiquitination by CBL regulates the receptor stability and activity through proteasomal degradation.
Similarity:
Belongs to the protein kinase superfamily. Tyr protein kinase family.
Contains 3 IPT/TIG domains.
Contains 1 protein kinase domain.
Contains 1 Sema domain.
Database links:
UniProtKB/Swiss-Prot: Q04912.2
Important Note:
This product as supplied is intended for research use only, not for use in human, therapeutic or diagnostic applications.
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