Reaction of tyrosyl-modifying reagents with the ligand- and DNA-binding domains of the rabbit liver glucocorticoid receptor.
We have studied the effects of p-nitrobenzenesulfonyl fluoride, 4-fluorosulfonyl-1-hydroxy-2-naphtoic acid, 7-chloro-4-nitrobenz-2-oxa-1,3-diazole and tetranitromethane on the glucocorticoid receptor from rabbit liver. Our results show that all tyrosine modifying reagents inhibit the binding of [3H]dexamethasone to the receptor. Equilibrium binding experiments revealed that only 4-fluorosulfonyl-1-hydroxy-2-naphtoic acid is a competitive inhibitor while the other chemical probes decrease the concentration of binding sites. Transformation of glucocorticoid-receptor complexes was markedly reduced when heat treatment was performed in the presence of tyrosyl-directed reagents. Taken together, these results indicate for the first time that critical tyrosyl moieties may be involved in both hormone binding and transformation of the glucocorticoid receptor.
Blanchardie
P
P
Université de Nantes, Faculté de Médecine CHR, Hôtel-Dieu Laboratoire de Biochimie, France.
Denis
M
M
Orsonneau
J L
JL
Lustenberger
P
P
D009327:4-Chloro-7-nitrobenzofurazan / Q000378:metabolism*; D000818:Animals; D001665:Binding Sites; D004247:DNA / Q000378:metabolism*; D003907:Dexamethasone / Q000378:metabolism; D007700:Kinetics; D008024:Ligands; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008697:Methane / Q000031:analogs & derivatives*; D009281:Naphthalenes / Q000378:metabolism*; D009578:Nitrobenzenes / Q000378:metabolism*; D010069:Oxadiazoles / Q000378:metabolism*; D011817:Rabbits; D011965:Receptors, Glucocorticoid / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D013774:Tetranitromethane / Q000378:metabolism*; D014443:Tyrosine / Q000031:analogs & derivatives / Q000494:pharmacology* / Q000502:physiology*
D008024:Ligands; D009281:Naphthalenes; D009578:Nitrobenzenes; D010069:Oxadiazoles; D011965:Receptors, Glucocorticoid; C034442:4-nitrobenzenesulfonyl fluoride; D014443:Tyrosine; D003907:Dexamethasone; C064823:4-fluorosulfonyl-1-hydroxy-2-naphthoic acid; D004247:DNA; D009327:4-Chloro-7-nitrobenzofurazan; D013774:Tetranitromethane; D008697:Methane