p185erbB2 Binds to GRP94 in Vivo

Abstract

Treatment of SKBr3 cells with benzoquinone ansamycins, such as geldanamycin (GA), depletes p185[IMG]_16856_tex2html_wrap104.xbm">, 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 p185[IMG]_16856_tex2html_wrap104.xbm"> correlates with their ability to compete with the photoaffinity label for binding to this protein. In this report, we present evidence that the[IMG] _16856_tex2html_wrap98.xbm">100-kDa ansamycin-binding protein is GRP94. Membrane-associated p185[IMG]_16856_tex2html_wrap104.xbm"> exists in a stable complex with GRP94. GA binding to GRP94 disrupts this complex, leading to degradation of pre-existing p185[IMG]_16856_tex2html_wrap104.xbm"> protein, and resulting in an altered subcellular distribution of newly synthesized p185[IMG]_16856_tex2html_wrap104.xbm">