PMID- 1718989 OWN - NLM STAT- MEDLINE DCOM- 19911226 LR - 20211203 IS - 0021-9258 (Print) IS - 0021-9258 (Linking) VI - 266 IP - 33 DP - 1991 Nov 25 TI - The tyrosine-phosphorylated hepatocyte growth factor/scatter factor receptor associates with phosphatidylinositol 3-kinase. PG - 22087-90 AB - The receptor for hepatocyte growth factor, also known as scatter factor (HGF/SF), has recently been identified as the 190-kDa heterodimeric tyrosine kinase encoded by the MET proto-oncogene (p190MET). The signaling pathway(s) triggered by HGF/SF are unknown. In A549 cells, a lung epithelial cell line, nanomolar concentrations of HGF/SF induced tyrosine phosphorylation of the p190MET receptor. The autophosphorylated receptor coprecipitated with phosphatidylinositol 3-kinase (PI 3-kinase) activity. In GTL16 cells, a cell line derived from a gastric carcinoma, the p190MET receptor, overexpressed and constitutively phosphorylated on tyrosine, coprecipitated with PI 3-kinase activity and with the 85-kDa PI 3-kinase subunit. In these cells activation of protein kinase C or the increase of intracellular [Ca2+] inhibits tyrosine phosphorylation of the p190MET receptor as well as the association with both PI 3-kinase activity and the 85-kDa subunit of the enzyme. In an in vitro assay, tyrosine phosphorylation of the immobilized p190MET receptor was required for binding of PI 3-kinase from cell lysates. These data strongly suggest that the signaling pathway activated by the HGF/SF receptor includes generation of D-3-phosphorylated inositol phospholipids. FAU - Graziani, A AU - Graziani A AD - Department of Biomedical Sciences and Oncology, University of Torino Medical School, Italy. FAU - Gramaglia, D AU - Gramaglia D FAU - Cantley, L C AU - Cantley LC FAU - Comoglio, P M AU - Comoglio PM LA - eng SI - GENBANK/X54559 GR - R01 GM041890/GM/NIGMS NIH HHS/United States GR - GM 36624/GM/NIGMS NIH HHS/United States GR - GM 41890/GM/NIGMS NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - J Biol Chem JT - The Journal of biological chemistry JID - 2985121R RN - 0 (Growth Substances) RN - 0 (MAS1 protein, human) RN - 0 (Macromolecular Substances) RN - 0 (Proto-Oncogene Mas) RN - 0 (Receptors, Cell Surface) RN - 21820-51-9 (Phosphotyrosine) RN - 42HK56048U (Tyrosine) RN - 67256-21-7 (Hepatocyte Growth Factor) RN - EC 2.7.- (Phosphotransferases) RN - EC 2.7.10.1 (Proto-Oncogene Proteins c-met) RN - EC 2.7.11.13 (Protein Kinase C) SB - IM MH - Cell Line MH - Growth Substances/isolation & purification/*metabolism MH - Hepatocyte Growth Factor MH - Humans MH - Macromolecular Substances MH - Molecular Sequence Data MH - Molecular Weight MH - Phosphatidylinositol 3-Kinases MH - Phosphorylation MH - Phosphotransferases/*metabolism MH - Phosphotyrosine MH - Protein Binding MH - Protein Kinase C/metabolism MH - Proto-Oncogene Mas MH - Proto-Oncogene Proteins c-met MH - Proto-Oncogenes MH - Receptors, Cell Surface/*metabolism MH - Tyrosine/*analogs & derivatives/analysis EDAT- 1991/11/25 00:00 MHDA- 1991/11/25 00:01 CRDT- 1991/11/25 00:00 PHST- 1991/11/25 00:00 [pubmed] PHST- 1991/11/25 00:01 [medline] PHST- 1991/11/25 00:00 [entrez] AID - S0021-9258(18)54536-1 [pii] PST - ppublish SO - J Biol Chem. 1991 Nov 25;266(33):22087-90.