Protein tyrosine phosphatase PTP-S binds to the juxtamembrane region of the hepatocyte growth factor receptor Met.

摘要: We reported previously that a protein tyrosine phosphatase (PTP) activity is associated with the immunoprecipitated hepatocyte growth factor (HGF) receptor, also known as Met. The increased reversibly when Met was stimulated by HGF and decreased inactivated PMA. To identify PTP-binding region, we used deletion mutants of receptor beta-subunit. PTP did not associate Tpr-Met, construct containing residues 1010-1390 fused to Tpr. In contrast, present expressed contained full juxtamembrane region (residues 956-1390 Met) or part this 957-1390 995-1390), indicating between 995 1009. This includes Tyr1003, site involved in downstream signalling. Incubation from GTL-16 cells an 8-mer phosphopeptide derived 1003-1010 induced marked decrease activity, suggesting peptide reproduced region. Mutation Glu, Asp Arg at positions -4, -1 +1 respectively relative Tyr1003 9-mer 999-1007) abolished ability Phosphorylation required for binding, since: (1) both phospho- dephospho-peptides on solid bead bound cell extract, (2) mutant lacking 1-955 which had been changed into Phe. order partially purify affinity column prepared using Met-derived comprising 998-1007. Less than 0.1% total cellular retained column, eluted low salt concentrations. Using antibodies, identified PTP-S, soluble epithelial fibroblasts.