IDENTIFICATION OF A GROUP OF SER-PRO MOTIF HORMONE-INDUCIBLE PHOSPHORYLATION SITES IN THE HUMAN PROGESTERONE-RECEPTOR

The human progesterone receptor (PR) is a member of the steroid/thyroid hormone superfamily of nuclear receptors. The receptor is expressed as two forms, PR-B and the shorter PR-A, which lacks the NC IP-terminal 164 amino acids of PR-a; whereas PR-B seems to be predominantly a transcriptional activator, PR-A also functions as a repressor. Our previous studies of PR expressed in T47D breast cancer cells have shown that PR is a phosphoprotein whose phosphorylation is enhanced in response to hormone. There is an initial rapid (minutes) increase in phosphorylation followed by a slower, less substantial increase, which results in decreased mobility of the receptor on sodium dodecyl sulfate gels. We now report the identification of three phosphorylation sites, which are predominantly phosphorylated during the later phase of the response to hormone. These sites, Ser(102), Ser(294), and Ser(345), are all found in Ser-Pro consensus sequences. Whereas Ser(294) and Ser(345) are common to PR-A and PR-B, Ser(102) is unique to PR-a. Finally, we demonstrate that phosphorylation of Ser(345) is associated with the altered mobility on sodium dodecyl sulfate gels.