| Abstract
| - Hsp90 and p50cdc37 provide a poorly understood biochemical function essential to certain proteinkinases, and recent models describe p50cdc37 as an exclusive hsp90 cohort which links hsp90 machineryto client kinases. We describe here the recovery of p50cdc37 in immunoadsorptions directed against thehsp90 cohorts FKBP52, cyp40, p60HOP, hsp70, and p23. Additionally, monoclonal antibodies againstFKBP52 coadsorb maturation intermediates of the hsp90-dependent kinases p56lck and HRI, and the presenceof these maturation intermediates significantly increases the representation of p50cdc37 and hsp90 on FKPB52machinery. Although the native heterocomplex between hsp90 and p50cdc37 is salt-labile, their dynamicinteractions with kinase substrates produce kinase−chaperone heterocomplexes which are highly salt-resistant. The hsp90 inhibitor geldanamycin does not directly disrupt the native association of hsp90 withp50cdc37 per se, but does result in the formation of salt-labile hsp90−kinase heterocomplexes which lackthe p50cdc37 cohort. We conclude that p50cdc37 does not simply serve as a passive structural bridge betweenhsp90 and its kinase substrates; instead, p50cdc37 is a nonexclusive hsp90 cohort which responds to hsp90'snucleotide-regulated conformational switching during the generation of high-affinity interactions withinthe hsp90−kinase−p50cdc37 heterocomplex.
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