Synthetic peptides derived from the steroid binding domain block modulator and molybdate action toward the rat glucocorticoid receptor.
Modulators are endogenous low-mol-wt inhibitors of glucocorticoid receptor activation, and are mimicked by exogenous sodium molybdate. Activation involves the dissociation of the 90-kDa heat-shock protein from the receptor. The heat-shock protein is thought to bind to a conserved 20-amino-acid region in the steroid-binding domain of the receptor (595-614 of the rat protein). Synthetic peptides corresponding to this amino acid sequence prevented the modulators and sodium molybdate from inhibiting receptor activation. These results imply that the region 595-614 of the rat glucocorticoid receptor is also a modulator/molybdate binding site.
Bodine
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Women's Health Research Institute, Wyeth-Ayerst Laboratories, Radnor, PA 19087, USA.
Alnemri
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ES
Litwack
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G
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D004305:Dose-Response Relationship, Drug; D008969:Molecular Sequence Data; D008982:Molybdenum / Q000494:pharmacology*; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000494:pharmacology*; D010742:Phospholipid Ethers / Q000494:pharmacology*; D051381:Rats; D011965:Receptors, Glucocorticoid / Q000037:antagonists & inhibitors*; D014222:Triamcinolone Acetonide / Q000378:metabolism
D010446:Peptide Fragments; D010742:Phospholipid Ethers; D011965:Receptors, Glucocorticoid; C055044:glucocorticoid receptor complex modulator; D008982:Molybdenum; C024687:sodium molybdate(VI); D014222:Triamcinolone Acetonide