Interaction of Hsp90 with the Nascent Form of the Mutant Epidermal Growth Factor Receptor EGFRvIII
作者： Sylvie J. Lavictoire , Doris A. E. Parolin , Alex C. Klimowicz , John F. Kelly , Ian A. J. Lorimer
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摘要: EGFRvIII is a mutant epidermal growth factor that promotes aggressive of glioblastomas. We made plasmid directed the expression an with three copies Flag epitope at its amino terminus. Flag-tagged was expressed same levels as unmodified EGFRvIII, and showed subcellular localization. However, could only be detected on present in endoplasmic reticulum; covalently modified during trafficking receptor through Golgi so it no longer recognized by anti-Flag antibody. This property exploited to selectively purify nascent from glioblastoma cells. Nascent found copurify set other proteins, identified mass spectrometry two reticulum chaperones Grp94 BiP, cytosolic Hsc70 Hsp90. The Hsp90-associated chaperone Cdc37 also co-purified suggesting Hsp90 binds complex this protein. Geldanamycin radicicol, chemically unrelated inhibitors Hsp90, decreased These studies show associates Cdc37, association necessary maintain EGFRvIII.
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