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.
Obermeier
A
A
Department of Molecular Biology, Max-Planck-Institut für Biochemie, Martinsried, Germany.
Lammers
R
R
Wiesmüller
K H
KH
Jung
G
G
Schlessinger
J
J
Ullrich
A
A
D000595:Amino Acid Sequence; D001483:Base Sequence; D001665:Binding Sites; D001667:Binding, Competitive; D002460:Cell Line; D006801:Humans; D066298:In Vitro Techniques; D046911:Macromolecular Substances; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009838:Oligodeoxyribonucleotides / Q000737:chemistry; D010446:Peptide Fragments / Q000737:chemistry; D019869:Phosphatidylinositol 3-Kinases; D010750:Phosphoproteins / Q000378:metabolism; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism*; D020917:Receptor, trkA; D017475:Receptors, Nerve Growth Factor / Q000378:metabolism*; D015398:Signal Transduction; D013329:Structure-Activity Relationship
D046911:Macromolecular Substances; D009838:Oligodeoxyribonucleotides; D010446:Peptide Fragments; D010750:Phosphoproteins; D011506:Proteins; D011518:Proto-Oncogene Proteins; D017475:Receptors, Nerve Growth Factor; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor); D020794:Receptor Protein-Tyrosine Kinases; D020917:Receptor, trkA