The Receptor for the Hepatocyte Growth Factor-Scatter Factor: Ligand-Dependent and Phosphorylation-Dependent Regulation of Kinase Activity

摘要: Hepatocyte Growth Factor (HGF) and Scatter (SF) are identical molecules produced by the stromal fibroblats non-parenchimal cells of many organs also present in serum. HGF exerts an array activities on epitelial cells, i.e. mitogenesis, dissociation epithelial sheets, stimulation cell motility, promotion matrix invasion. The receptor for is tyrosine kinase encoded MET proto-oncogene. It widely expressed normal tissues as a 190 kDa heterodimer two disulfide-linked protein subunits. binding triggers autophosphorylation β subunit intact cultured cells. Autophosphorylation upregulates activity receptor, increasing Vmax phosphotransfer reaction. major phosphorylation site has been mapped to Tyr 1235. Negative regulation occurs through distinguishable pathways involving C activation or increase intracellular Ca2+ concentration. Both lead serine residue(s) unique tryptic phosphopeptide decrease its activity. Receptor signal transduction inside target phosphorylated associates phosphatidylinositol 3-kinase, indicating that generation D-3 inositol lipids involved effecting motility and/or growth response HGF.