Native rat kidney mineralocorticoid receptor is a phosphoprotein whose transformation to a DNA-binding form is induced by phosphatases.

Addition of alkaline phosphatase to rat kidney cytosol diminishes the ability of the mineralocorticoid receptor (MR) to bind aldosterone in a time-, temperature- and concentration-dependent form. A variety of phosphatase inhibitors, including levamisole, are effective in preventing this inactivation. On the other hand, when the steroid-receptor complex is incubated in the presence of alkaline phosphatase, an increment in the rate of receptor transformation is evidenced by a change in the sedimentation coefficient from 8.8 S to 5.1 S, as well as increased DNA-binding capacity. The effects of alkaline phosphatase on activation and transformation can also be observed when the MR is incubated at 20 degreesC in the cytosolic medium, indicating that the catalytic action of an endogenous phosphatase may be involved in the transformation process. The ability of phosphatase inhibitors such as levamisole for suppressing both alkaline phosphatase- and endogenous phosphatase-directed transformation does not correspond well between them. Evidence is presented to affirm that the endogenous phosphatase activity is not due to an alkaline phosphatase-type, but it may be due to a protein serine/threonine phosphatase, as evidenced by the inhibitory effects of okadaic acid. The experimental results also show direct evidence that the MR undergoes phosphorylation in a physiological milieu.