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Identification of c‐erbB‐3 binding sites for phosphatidylinositol 3′‐kinase and SHC using an EGF receptor/c‐erbB‐3 chimera.
Author(s) -
Prigent S.A.,
Gullick W.J.
Publication year - 1994
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1002/j.1460-2075.1994.tb06577.x
Subject(s) - erbb , biology , epidermal growth factor , phosphorylation , grb2 , receptor tyrosine kinase , receptor , tyrosine kinase , phosphatidylinositol , tropomyosin receptor kinase c , ror1 , microbiology and biotechnology , signal transduction , biochemistry , platelet derived growth factor receptor , growth factor
c‐erbB‐3 is a member of the type I (EGF receptor‐related) family of growth factor receptors for which no ligand has been identified. To facilitate ligand stimulation we have constructed a chimeric receptor which possesses an activatable kinase and promotes the growth of NIH 3T3 fibroblasts. In this study we have shown that SHC and phosphatidylinositol 3′‐kinase bind to the activated EGF receptor/c‐erbB‐3 chimera. Whereas p85 is not phosphorylated to a significant extent, SHC appears to be a major substrate for phosphorylation on tyrosine. In contrast to EGF receptor and c‐erbB‐2, we were unable to detect binding of activated c‐erbB‐3 to GRB2. Using synthetic peptides corresponding to each of 13 potential phosphorylation sites on c‐erbB‐3, we have shown that tyrosine 1309 is responsible for SHC binding. Peptides containing the motif YXXM inhibit p85 association. By comparison with recently reported SHC binding sites on Middle T antigen and Trk we have identified a SHC binding motif, NPXY.