Transformation of glucocorticoid receptors bound to the antagonist RU 486: Effects of alkaline phosphatase
- Salk Institute for Biological Studies, San Diego, CA (USA)
RU 486 is a synthetic steroid that binds avidly to glucocorticoid receptors without promoting their transformation into activated transcription factors. A significant part of this behavior has been shown to be due to a failure of the RU 486 bound receptor to be efficiently released from a larger (sedimenting at 8-9 S) multimeric complex containing the 90-kDa heat shock protein. The studies have found that in vitro at 15{degree}C the RU 486-receptor was slowly released from the 8-9S complex and converted into a DNA binding protein by a process that could be blocked by sodium fluoride. Moreover, this transition was significantly accelerated by treatment with alkaline phosphatase. High-resolution anion-exchange chromatography showed that the profile of receptor subspecies released from the 8-9S complex was different for the RU 486 bound receptor when compared to the receptor occupied by the agonist triamcinolone acetonide. Production of the earliest eluting receptor form (peak A) was inhibited with RU 486. Treatment of the Ru 486-receptor with alkaline phosphatase increased the formation of the peak A subspecies as well as the capacity of receptor to bind DNA-cellulose. Taken together, the results indicate that phosphorylation of the receptor or a tightly bound factor contributes to defining the capacity with which individual steroids can promote dissociation of the 8-9S complex and conversion of the glucocorticoid receptor into a DNA-binding protein.
- OSTI ID:
- 6056986
- Journal Information:
- Biochemistry; (USA), Vol. 29:34; ISSN 0006-2960
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
ALKALINE PHOSPHATASE
BIOLOGICAL EFFECTS
RECEPTORS
CONFORMATIONAL CHANGES
TRANSCRIPTION FACTORS
AUTORADIOGRAPHY
GLUCOCORTICOIDS
ION EXCHANGE CHROMATOGRAPHY
MESSENGER-RNA
PHOSPHORYLATION
POST-TRANSLATION MODIFICATION
RECOMBINANT DNA
STEROIDS
TRITIUM COMPOUNDS
ADRENAL HORMONES
CHEMICAL REACTIONS
CHROMATOGRAPHY
CORTICOSTEROIDS
DNA
ENZYMES
ESTERASES
HYDROGEN COMPOUNDS
HYDROLASES
HYDROXY COMPOUNDS
KETONES
MEMBRANE PROTEINS
NUCLEIC ACIDS
NUCLEOPROTEINS
ORGANIC COMPOUNDS
PHOSPHATASES
PREGNANES
PROTEINS
RNA
SEPARATION PROCESSES
550201* - Biochemistry- Tracer Techniques