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

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.
Mesh Terms:
1-Phosphatidylinositol 3-Kinase, Adaptor Proteins, Signal Transducing, Amino Acid Sequence, Animals, Base Sequence, Cattle, Cells, Cultured, DNA, Complementary, Escherichia coli, GRB2 Adaptor Protein, Gene Library, Humans, Molecular Sequence Data, Phosphotransferases (Alcohol Group Acceptor), Platelet-Derived Growth Factor, Precipitin Tests, Protein Binding, Protein Conformation, Proteins, Rats, Recombinant Fusion Proteins, Selection, Genetic, Sequence Analysis, DNA, Signal Transduction, Yeasts
J. Biol. Chem.
Date: May. 26, 1995
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