ABSTRACT
In this chapter, the authors review the evidence that the glucocorticoid receptor is composed of phosphoproteins. They discuss experiments that suggest the active, ligand-binding state of the receptor may be regulated by a phosphorylation dephosphorylation mechanism. The authors describe the evidence for thioredoxin-mediated receptor reduction and how phosphorylation and reduction of receptors may interact to determine the steroid-binding state of the glucocorticoid receptor. The stoichiometry of the 90- and 100-kdalton phosphoproteins in the untransformed complex is not known, and it is possible that other nonsteroid-binding proteins that have not yet been identified are also components of the untransformed receptor complex. Several groups have demonstrated the energy requirement for maintaining high-affinity glucocorticoid-binding capacity in intact cells. Molybdate-stabilized glucocorticoid observations support a general model in which untransformed steroid receptors are associated with one or more 90-kdalton nonsteroid-binding phosphoproteins. Taken together, these observations describe very well the 90-kdalton murine heat-shock protein (hsp 90) as a likely candidate for the receptor-associated protein.
