Agonist-induced association of the p21ras GTPase-activating protein with phosphatidylinositol 3-kinase

Biochem Biophys Res Commun. 1992 Dec 30;189(3):1503-8. doi: 10.1016/0006-291x(92)90245-g.

Abstract

The signal transduction properties of the 21-kDa GTP-binding proteins, encoded by the ras genes, are only partly known. In a recent report, we demonstrated that the signaling pathway of p21ras, like that of several growth factors, is closely associated with phosphatidylinositol 3-kinase (PtdIns 3-kinase) activity. We showed that insulin-like growth factor-1 (IGF-1) and insulin increased the phosphatidylinositol 3-kinase activity in immunoprecipitates obtained with anti-phosphotyrosine and anti-ras antibodies in Ha-ras-transformed epithelial cells. Several findings in this previous study suggested that an additional protein was likely to be associated with the PtdIns 3-kinase. The suggestion that p21ras GTPase-activating protein (GAP) acts not only as a regulator of p21ras activity but also as a direct downstream target in the signaling pathway of p21ras led us to investigate the possible association of PtdIns 3-kinase with GAP. The stimulation of Ha-ras-transformed epithelial cells with IGF-1 caused an increased association of PtdIns 3-kinase activity with GAP, as seen by immunoprecipitation with anti-p21ras and anti-GAP antibodies. The 85-kDa regulatory subunit of PtdIns 3-kinase was present in immunoprecipitates obtained with antibodies against GAP and p21ras of IGF-1 stimulated cells. These data suggest that GAP acts as a downstream target for p21ras via its association with PtdIns 3-kinase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Western
  • Cell Line
  • Cell Transformation, Neoplastic
  • Epithelium
  • GTPase-Activating Proteins
  • Genes, ras*
  • Insulin-Like Growth Factor I / pharmacology*
  • Kinetics
  • Liver
  • Phosphatidylinositol 3-Kinases
  • Phosphotransferases / isolation & purification
  • Phosphotransferases / metabolism*
  • Protein Binding
  • Proteins / isolation & purification
  • Proteins / metabolism*
  • Rats
  • Rats, Inbred F344
  • ras GTPase-Activating Proteins

Substances

  • GTPase-Activating Proteins
  • Proteins
  • ras GTPase-Activating Proteins
  • Insulin-Like Growth Factor I
  • Phosphotransferases
  • Phosphatidylinositol 3-Kinases