Direct association of Grb2 with the p85 subunit of phosphatidylinositol 3-kinase

J Biol Chem. 1995 May 26;270(21):12774-80. doi: 10.1074/jbc.270.21.12774.


Phosphatidylinositol 3-kinase (PI 3-kinase) has been shown to play a key role in growth factor signaling pathways, although its signaling mechanism has not been fully elucidated. Using the yeast interaction trap system, we have identified Grb2 as a PI 3-kinase interacting protein. Our experiments demonstrate that p85, the regulatory subunit of PI 3-kinase, interacts with Grb2 in vivo, and this interaction is independent of growth factor stimulation. The direct association between Grb2 and p85 was reconstituted in vitro with glutathione S-transferase fusion proteins. Domain analyses and peptide competition indicate that the association is mediated by the SH3 domains of Grb2 and the proline-rich motifs of p85 and that only one SH3 domain is required for minimal binding. The interaction does not displace the catalytic subunit of PI 3-kinase but is exclusive of Sos. Signaling through PI 3-kinase, therefore, may involve the ubiquitous adapter Grb2, which serves as a convergence point for multiple pathways.

Publication types

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

MeSH terms

  • Adaptor Proteins, Signal Transducing*
  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Cattle
  • Cells, Cultured
  • DNA, Complementary / genetics
  • Escherichia coli / genetics
  • GRB2 Adaptor Protein
  • Gene Library
  • Humans
  • Molecular Sequence Data
  • Phosphatidylinositol 3-Kinases
  • Phosphotransferases (Alcohol Group Acceptor) / genetics
  • Phosphotransferases (Alcohol Group Acceptor) / immunology
  • Phosphotransferases (Alcohol Group Acceptor) / metabolism*
  • Platelet-Derived Growth Factor / pharmacology
  • Precipitin Tests
  • Protein Binding
  • Protein Conformation
  • Proteins / genetics
  • Proteins / metabolism*
  • Rats
  • Recombinant Fusion Proteins / metabolism
  • Selection, Genetic
  • Sequence Analysis, DNA
  • Signal Transduction / physiology*
  • Yeasts / genetics


  • Adaptor Proteins, Signal Transducing
  • DNA, Complementary
  • GRB2 Adaptor Protein
  • GRB2 protein, human
  • Grb2 protein, rat
  • Platelet-Derived Growth Factor
  • Proteins
  • Recombinant Fusion Proteins
  • Phosphotransferases (Alcohol Group Acceptor)