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• W2047797038 endingPage "18995" @default.
• W2047797038 startingPage "18989" @default.
• W2047797038 abstract "The 180-kDa transmembrane tyrosine kinase ErbB-4 is a receptor for the growth factor heregulin. 125I-Heregulin binding to NIH 3T3 cells overexpressing the ErbB-4 receptor is rapidly decreased by 12-O-tetradecanoylphorbol-13-acetate (TPA) pretreatment. Immunologic analysis demonstrates that TPA treatment of cells induces the proteolytic cleavage of ErbB-4, producing an 80-kDa cytoplasmic domain fragment, which contains a low level of phosphotyrosine, and a 120-kDa ectodomain fragment, which is released into the extracellular medium. Cleavage of ErbB-4 was also enhanced by other protein kinase C activators, i.e. platelet-derived growth factor, ionomycin, and synthetic diacylglycerol, while protein kinase C inhibition or down-regulation suppressed the TPA stimulation of ErbB-4 degradation. TPA did not induce the degradation of related receptors (ErbB-1, ErbB-2, and ErbB-3) in the EGF receptor family. The phorbol ester-induced cleavage of ErbB-4 occurs within or close to the ectodomain, as the 80-kDa cytoplasmic domain fragment is recognized by antibody to the ErbB-4 carboxyl terminus and is membrane-associated. Coprecipitation experiments show that, while the 80-kDa ErbB-4 fragment is associated with the SH2-containing molecules PLC-γ1 and Shc, TPA did not induce the phosphorylation of these substrates in intact cells. In addition, kinase assays in vitro indicate that the 80-kDa fragment is not an active tyrosine kinase. These results show that protein kinase C negatively regulates heregulin signaling through the ErbB-4 receptor by the activation of a selective proteolytic mechanism." @default.
• W2047797038 created "2016-06-24" @default.
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• W2047797038 date "1996-08-01" @default.
• W2047797038 modified "2023-10-18" @default.
• W2047797038 title "Selective Cleavage of the Heregulin Receptor ErbB-4 by Protein Kinase C Activation" @default.
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• W2047797038 doi "https://doi.org/10.1074/jbc.271.31.18989" @default.
• W2047797038 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/8702564" @default.
• W2047797038 hasPublicationYear "1996" @default.
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