Tyrosines1234-1235 are critical for activation of the tyrosine kinase encoded by the MET proto-oncogene (HGF receptor).

摘要: The tyrosine kinase encoded by the MET proto-oncogene (p190MET) is receptor for Hepatocyte Growth Factor/Scatter Factor (HGF/SF). Previous work has shown that autophosphorylation of p190MET enhances its enzymatic activity and major phosphorylation site Tyr1235, located in catalytic domain. This residue part a 'three tyrosine' motif, including Tyr1230, Tyr1234, conserved several other kinases. We studied role these tyrosines positive regulation site-directed mutagenesis. Substitution either Tyr1235 or Tyr1234 with phenylalanine severely reduced vitro toward exogenous substrates. Kinetic experiments showed residual mutants could still be enhanced autophosphorylation. Phosphopeptide mapping indicated that, absence phosphorylated. Only replacement both yielded mutant which completely lost ability to activated In stable transfectants expressing HGF/SF single substitution response was impaired. ligand did not induce nor stimulated chemotaxis. These data show are critical activation intact cells.