Polyubiquitination and Proteasomal Degradation of the p185c-B-2 Receptor Protein-tyrosine Kinase Induced by Geldanamycin

Abstract excerpt

Treatment of SKBr3 human breast carcinoma cells with the benzoquinoid ansamycin, geldanamycin, rapidly depletes p185c-erbB-2 protein-tyrosine kinase. Loss of p185c-erbB-2 is initiated by disruption of a heteromeric complex between p185c-erbB-2 and the 94-kDa glucose-regulated protein, GRP94, to which geldanamycin binds avidly. Here we report that within minutes of exposure to geldanamycin, mature p185c-erbB-2...

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