Autophosphorylation promotes complex formation of recombinant hepatocyte growth factor receptor with cytoplasmic effectors containing SH2 domains.

摘要: Hepatocyte growth factor (HGF), also known as scatter (SF), is a polypeptide which induces motility and/or mitogenesis in epithelial cells. The receptor for HGF/SF, p190MET, two-chain transmembrane tyrosine kinase encoded by the MET proto-oncogene. To identify cytoplasmic effectors involved signal transduction we have produced human HGF/SF insect cells (Sf9) means of recombinant baculovirus. Two 170-kDa forms were synthesized Sf9 cells: uncleaved single-chain precursor (which far more abundant) and proteolytically processed molecule. Both species are phosphorylated on vivo active kinases vitro. binds phosphorylates vitro four transducers containing src homology region 2 (SH2) domains: 85-kDa subunit phosphatidylinositol 3-kinase (Pl 3-kinase), rasGAP, phospholipase-C gamma (PLC-gamma), p59Fyn, family. In all cases association strictly dependent phosphorylation receptor, indicating that it occurs via specific interaction with SH2 domains. These results show has sequence requirements binding spectrum whose different combinations target may result observed pleiotropic biological response.