Identification of Trk binding sites for SHC and phosphatidylinositol 3'-kinase and formation of a multimeric signaling complex.

Phosphotyrosine-containing synthetic peptides were used to identify the binding sites for cellular polypeptides involved in nerve growth factor receptor/Trk-mediated signal transduction. In vitro association of SHC and the p85 subunit of phosphatidylinositol 3'-kinase with the Trk tyrosine kinase was prevented only by phosphorylated Y-490- and Y-751-containing peptides, respectively. In spite of the close proximity of the p85 binding site to that of phospholipase C gamma (Y-785), both target proteins are able to interact with the same receptor molecule simultaneously.