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Titolo:
GLUCOCORTICOID RECEPTORS IN ATP-DEPLETED CELLS - DEPHOSPHORYLATION, LOSS OF HORMONE-BINDING, HSP90 DISSOCIATION, AND ATP-DEPENDENT CYCLING
Autore:
HU LM; BODWELL J; HUO JM; ORTI E; MUNCK A;
Indirizzi:
DARTMOUTH COLL SCH MED,DEPT PHYSIOL LEBANON NH 03756 DARTMOUTH COLL SCH MED,DEPT PHYSIOL LEBANON NH 03756
Titolo Testata:
The Journal of biological chemistry
fascicolo: 9, volume: 269, anno: 1994,
pagine: 6571 - 6577
SICI:
0021-9258(1994)269:9<6571:GRIAC->2.0.ZU;2-N
Fonte:
ISI
Lingua:
ENG
Soggetto:
HEAT-SHOCK PROTEIN; SITE-SPECIFIC MUTAGENESIS; RAT THYMUS-CELLS; PROGESTERONE-RECEPTOR; PHENOTYPIC SELECTION; NUCLEAR MATRIX; INTACT-CELLS; PHOSPHORYLATION; COMPLEXES; MODEL;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
40
Recensione:
Indirizzi per estratti:
Citazione:
L.M. Hu et al., "GLUCOCORTICOID RECEPTORS IN ATP-DEPLETED CELLS - DEPHOSPHORYLATION, LOSS OF HORMONE-BINDING, HSP90 DISSOCIATION, AND ATP-DEPENDENT CYCLING", The Journal of biological chemistry, 269(9), 1994, pp. 6571-6577

Abstract

Dependence of hormone binding to glucocorticoid receptors (GRs) on cellular ATP levels suggested that GRs traverse an ATP-dependent cycle, and without ATP accumulate in forms that cannot bind hormone. Such ''null'' receptors (NRs) were identified in ATP-depleted WEHI-7 cells, where they are tightly associated with the nuclear fraction and partly dephosphorylated. With WCL2 cells (Chinese hamster ovary cells with overexpressed GRs) depleted of ATP with azide, we have now identified dephosphorylated sites on NRs, studied possible roles of phosphorylation using GR mutants, and measured association with the 90-kDa heat shock protein (hsp90). Most NRs in WCL2 cells are dephosphorylated at serines 220 and 234, but G;Rs with those serines mutated to alanines do not resemble NRs since they bind hormone. They do not associate strongly with nuclei. On azide treatment, however, mutated GRs lose hormone binding capacity faster than normal GRs. Association of hsp90 (and presumably other heat shock proteins) with cytosolic GRs is drastically reduced by azide treatment, sufficient to account for decreased hormone binding. We conclude that: (a) dephosphorylation of GRs does not yield NRs, but may weaken association with hsp90. (b) The postulated ATP-dependent GR cycle can be accounted for by dissociation, and ATP-dependent reconstitution, of GR.hsp90 complexes. (c) ATP depletion blocks reconstitution of complexes. Uncomplexed GRs may accumulate as one form of NR; they are probably also the precursors for other forms of NR.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 24/09/20 alle ore 09:59:19