Chavany C, Mimnaugh E, Miller P, Bitton R, Nguyen P, Trepel J, Whitesell L, Schnur R, Moyer J, Neckers L
Clinical Pharmacology Branch and Medicine Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
J Biol Chem. 1996 Mar 1;271(9):4974-7. doi: 10.1074/jbc.271.9.4974.
Treatment of SKBr3 cells with benzoquinone ansamycins, such as geldanamycin (GA), depletes p185erbB2, the receptor tyrosine kinase encoded by the erbB2 gene. In the same cells, a biologically active benzoquinone photoaffinity label specifically binds a protein of about 100 kDa, and the ability of various GA derivatives to reduce the intracellular level of p185erbB2 correlates with their ability to compete with the photoaffinity label for binding to this protein. In this report, we present evidence that the approximately 100-kDa ansamycin-binding protein is GRP94. Membrane-associated p185erbB2 exists in a stable complex with GRP94. GA binding to GRP94 disrupts this complex, leading to degradation of pre-existing p185erbB2 protein, and resulting in an altered subcellular distribution of newly synthesized p185erbB2.
用苯醌安莎霉素（如格尔德霉素，GA）处理SKBr3细胞，可使erbB2基因编码的受体酪氨酸激酶p185erbB2减少。在相同细胞中，一种具有生物活性的苯醌光亲和标记物能特异性结合一种约100 kDa的蛋白质，各种GA衍生物降低细胞内p185erbB2水平的能力与其与光亲和标记物竞争结合该蛋白质的能力相关。在本报告中，我们提供证据表明，约100 kDa的安莎霉素结合蛋白是GRP94。膜相关的p185erbB2与GRP94形成稳定复合物。GA与GRP94结合会破坏该复合物，导致预先存在的p185erbB2蛋白降解，并使新合成的p185erbB2的亚细胞分布发生改变。
