Abstract
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.
MeSH terms
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Adaptor Proteins, Signal Transducing*
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Amino Acid Sequence
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Animals
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Avian Proteins*
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Base Sequence
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Cell Adhesion
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Cells, Cultured
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Cytoskeletal Proteins / metabolism
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ErbB Receptors / genetics
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ErbB Receptors / metabolism*
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GRB2 Adaptor Protein
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Glutathione Transferase / genetics
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Glutathione Transferase / metabolism
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Molecular Sequence Data
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Phosphatidylinositol 3-Kinases
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Phosphopeptides / genetics
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Phosphoproteins / metabolism
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Phosphorylation
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Phosphotransferases (Alcohol Group Acceptor) / metabolism*
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Protein Binding
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Proteins / genetics
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Proteins / metabolism
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Proto-Oncogene Proteins / genetics
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Proto-Oncogene Proteins / metabolism*
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Recombinant Fusion Proteins / metabolism
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Second Messenger Systems*
Substances
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Adaptor Proteins, Signal Transducing
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Avian Proteins
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Cytoskeletal Proteins
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GRB2 Adaptor Protein
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Phosphopeptides
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Phosphoproteins
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Proteins
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Proto-Oncogene Proteins
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Recombinant Fusion Proteins
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cytoskeletal p85 protein, chicken
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Glutathione Transferase
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Phosphatidylinositol 3-Kinases
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Phosphotransferases (Alcohol Group Acceptor)
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ErbB Receptors