The tyrosine-phosphorylated hepatocyte growth factor/scatter factor receptor associates with phosphatidylinositol 3-kinase

J Biol Chem. 1991 Nov 25;266(33):22087-90.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Cell Line
  • Growth Substances / isolation & purification
  • Growth Substances / metabolism*
  • Hepatocyte Growth Factor
  • Humans
  • Macromolecular Substances
  • Molecular Sequence Data
  • Molecular Weight
  • Phosphatidylinositol 3-Kinases
  • Phosphorylation
  • Phosphotransferases / metabolism*
  • Phosphotyrosine
  • Protein Binding
  • Protein Kinase C / metabolism
  • Proto-Oncogene Mas
  • Proto-Oncogene Proteins c-met
  • Proto-Oncogenes
  • Receptors, Cell Surface / metabolism*
  • Tyrosine / analogs & derivatives*
  • Tyrosine / analysis


  • Growth Substances
  • MAS1 protein, human
  • Macromolecular Substances
  • Proto-Oncogene Mas
  • Receptors, Cell Surface
  • Phosphotyrosine
  • Tyrosine
  • Hepatocyte Growth Factor
  • Phosphotransferases
  • Proto-Oncogene Proteins c-met
  • Protein Kinase C

Associated data

  • GENBANK/X54559