PMID- 7688741 OWN - NLM STAT- MEDLINE DCOM- 19930916 LR - 20210210 IS - 0021-9258 (Print) IS - 0021-9258 (Linking) VI - 268 IP - 24 DP - 1993 Aug 25 TI - A protein tyrosine phosphatase activity associated with the hepatocyte growth factor/scatter factor receptor. PG - 18176-80 AB - The receptor for the growth and motility factor, hepatocyte growth factor/scatter factor (HGF/SF), is a transmembrane tyrosine kinase encoded by the MET oncogene. Previous work has shown that receptor phosphorylation on tyrosine is critical for both kinase activation and association with intracellular signal transducers. In this paper, we report that a protein tyrosine phosphatase activity (PTP) coprecipitates with the HGF/SF receptor. The associated PTP activity correlates with the kinase activation of the receptor, increasing up to 5-fold over the basal 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 from cells where the MET oncogene is amplified and overexpressed. In these cells, a parallel decrease in PTP activity is observed after inhibition of receptor tyrosine phosphorylation following protein kinase C activation. The associated PTP activity is effective in dephosphorylating the HGF/SF receptor. These data show that a protein tyrosine phosphatase is functionally coupled to the HGF/SF receptor. FAU - Villa-Moruzzi, E AU - Villa-Moruzzi E AD - Department of Experimental Biomedicine, University of Pisa, Italy. FAU - Lapi, S AU - Lapi S FAU - Prat, M AU - Prat M FAU - Gaudino, G AU - Gaudino G FAU - Comoglio, P M AU - Comoglio PM LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - J Biol Chem JT - The Journal of biological chemistry JID - 2985121R RN - 0 (Proto-Oncogene Proteins) RN - 0 (Recombinant Proteins) RN - 21820-51-9 (Phosphotyrosine) RN - 42HK56048U (Tyrosine) RN - 67256-21-7 (Hepatocyte Growth Factor) RN - EC 2.7.10.1 (Protein-Tyrosine Kinases) RN - EC 2.7.10.1 (Proto-Oncogene Proteins c-met) RN - EC 2.7.11.13 (Protein Kinase C) RN - EC 3.1.3.48 (Protein Tyrosine Phosphatases) SB - IM MH - Cell Line MH - Cell Membrane MH - Chromatography, Gel MH - Gene Expression MH - Hepatocyte Growth Factor/*metabolism/pharmacology MH - Humans MH - Kinetics MH - Oncogenes MH - Phosphotyrosine MH - Protein Kinase C/metabolism MH - Protein Tyrosine Phosphatases/isolation & purification/*metabolism MH - Protein-Tyrosine Kinases/genetics/metabolism MH - Proto-Oncogene Proteins/genetics/isolation & purification/*metabolism MH - Proto-Oncogene Proteins c-met MH - Proto-Oncogenes MH - Recombinant Proteins/metabolism MH - Time Factors MH - Transfection MH - Tumor Cells, Cultured MH - Tyrosine/analogs & derivatives/metabolism EDAT- 1993/08/25 00:00 MHDA- 1993/08/25 00:01 CRDT- 1993/08/25 00:00 PHST- 1993/08/25 00:00 [pubmed] PHST- 1993/08/25 00:01 [medline] PHST- 1993/08/25 00:00 [entrez] AID - S0021-9258(17)46826-8 [pii] PST - ppublish SO - J Biol Chem. 1993 Aug 25;268(24):18176-80.