Several studies have suggested that steroid receptors can exist in phosphorylated and dephosphorylated forms. We have recently demonstrated that the non-transformed avian progesterone receptor is a phosphoprotein. This realization opens the way for a number of new and potentially exciting investigations regarding the dynamics and the significance of receptor phosphorylation. We propose to pursue this aspect of progesterone receptor characterization as follows: 1. The basic observation will be described more completely by quantitation of the extent and possible heterogeneity of receptor phosphorylation, and by analysis for more labile phosphorylation sites in addition to that observed previously. 2. Efforts will be made to identify dephosphorylated receptor forms that may relate to receptor activity. The effects of in vitro dephosphorylation on the binding and molecular properties of receptor will be studied and attempts will be made to identify and isolate specific phosphatases that may regulate receptor activity. 3. Using dephosphorylated receptor as a substrate, efforts will be made to phosphorylate the receptor in vitro with exogenous kinases. Attempts will also be made to identify and isolate endogenous kinases that phosphorylate the receptor and to study the effects of phosphorylation on receptor properties. These studies should provide a thorough framework for understanding the components and dynamics of the receptor phosphorylation/dephosphorylation system.
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