Regulation of glucocorticoid receptor function through assembly of a receptor-heat shock protein complex.
Incubation of immunopurified, hormone-free mouse glucocorticoid receptors with rabbit reticulocyte lysate results in ATP-dependent and monovalent cation-dependent assembly of the GR into a heterocomplex with hsp90, hsp70, and hsp56. Heterocomplex assembly is accompanied by conversion of the receptor from a form that does not bind steroid to a high affinity steroid-binding conformation. Reticulocyte lysate also promotes ATP-dependent dissociation of unliganded receptors from a prebound receptor-DNA complex. Receptor released from DNA has been reconstituted into the heat shock protein heterocomplex and converted to the non-DNA-binding state. The reticulocyte lysate also reconstitutes pp60v-src into a heterocomplex containing hsp90 and p50, both of which are components of the native heterocomplex form of the tyrosine kinase in cytoplasm. Although the c-Raf-1 serine/threonine kinase has never been found in native association with hsp90, it can be assembled into a heat shock protein heterocomplex by the ATP-dependent system in reticulocyte lysate.
Hutchison
K A
KA
Department of Pharmacology, University of Michigan Medical School, Ann Arbor 48109.
Scherrer
L C
LC
Czar
M J
MJ
Stancato
L F
LF
Chow
Y H
YH
Jove
R
R
Pratt
W B
WB
D000818:Animals; D002460:Cell Line; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000378:metabolism*; D051379:Mice; D051381:Rats; D011965:Receptors, Glucocorticoid / Q000378:metabolism* / Q000502:physiology
D004268:DNA-Binding Proteins; D006360:Heat-Shock Proteins; D011965:Receptors, Glucocorticoid; D004247:DNA