A PROTEIN-TYROSINE-PHOSPHATASE ACTIVITY ASSOCIATED WITH THE HEPATOCYTE GROWTH-FACTOR SCATTER FACTOR-RECEPTOR

The receptor for the growth and motility factor, hepatocyte growth fac tor/scatter factor (HGF/SF), is a transmembrane tyrosine kinase encode d by the MET oncogene. Previous work has shown that receptor phosphory lation on tyrosine is critical for both kinase activation and associat ion with intracellular signal transducers. In this paper, we report th at a protein tyrosine phosphatase activity (PTP) coprecipitates with t he HGF/SF receptor. The associated PTP activity correlates with the ki nase activation of the receptor, increasing up to 5-fold over the basa l level after HGF/SF stimulation. The increase is reversible and time- and dose-dependent. A comparable level of activity is associated with constitutively tyrosine-phosphorylated receptors immunoprecipitated f rom cells where the MET oncogene is amplified and overexpressed. In th ese cells, a parallel decrease in PTP activity is observed after inhib ition of receptor tyrosine phosphorylation following protein kinase C activation. The associated PTP activity is effective in dephosphorylat ing the HGF/SF receptor. These data show that a protein tyrosine phosp hatase is functionally coupled to the HGF/SF receptor.