Heregulin-dependent translocation and hyperphosphorylation of ErbB-2.
Previous data have shown that in several tumor cells lines the addition of heregulin results in the translocation of ErbB-4 to a detergent-insoluble membrane fraction where it is hypertyrosine phosphorylated. The data herein demonstrate that heregulin or betacellulin, but not EGF, promotes the rapid translocation of ErbB-2, the heterodimerization partner for ErbB-4, to the same detergent-insoluble fraction in T47 D mammary carcinoma cells. The translocation of ErbB-2 and ErbB-4, but not ErbB-3, to this detergent-insoluble fraction is readily detected 2 min after the addition of heregulin. ErbB-2 present in this detergent-insoluble membrane fraction is tyrosine phosphorylated to a level fourfold greater than the majority of cellular ErbB-2 present in the detergent-soluble membrane fraction. These results suggest the ligand-dependent formation of hyperphosphorylated ErbB-4/ErbB-2 dimers coordinate with translocation to a putative membrane microdomain.
Zhou
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Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, Tennessee, TN 37232-0146, USA.
Carpenter
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D066259:Betacellulin; D004815:Epidermal Growth Factor / Q000378:metabolism / Q000494:pharmacology; D066246:ErbB Receptors / Q000378:metabolism*; D006133:Growth Substances / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D008024:Ligands; D020890:Neuregulin-1 / Q000378:metabolism* / Q000494:pharmacology; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000378:metabolism; D021381:Protein Transport; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D020893:Receptor, ErbB-3 / Q000378:metabolism; D066247:Receptor, ErbB-4; D014407:Tumor Cells, Cultured
D066259:Betacellulin; D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D006133:Growth Substances; D036341:Intercellular Signaling Peptides and Proteins; D008024:Ligands; D020890:Neuregulin-1; D019000:Phosphotyrosine; D018719:Erb-b2 Receptor Tyrosine Kinases; D020893:Receptor, ErbB-3; D066247:Receptor, ErbB-4; C587851:BTC protein, human; C587689:ERBB4 protein, human