Accession Number : ADA315692
Title : Regulation of Agonist--and Antagonist--Mediated Activation of Human Progesterone Receptors by Phosphorylation.
Descriptive Note : Annual rept. 1 Jul 95-30 Jun 96,
Corporate Author : BAYLOR COLL OF MEDICINE HOUSTON TX
Personal Author(s) : Zhang, Yixian
PDF Url : ADA315692
Report Date : JUL 1996
Pagination or Media Count : 20
Abstract : The human progesterone receptor (hPR) in breast cancer cells (T47D) is phosphorylated on multiple serine residues. I have previously reported the identification of eight phosphorylation sites. Here I show the identification of a new site, Ser2O. This site is hPR-B specific and contains a Ser-Pro consensus sequence. The role of phosphorylation in hPR and RU 486 antagonist/agonist switch has also been investigated. Using a yeast system, the effect of B-specific phosphorylation on AF3 transactivation has been studied. Mutation of Ser102 to Ala nearly depleted the activity of AF3, suggesting that phosphorylation is a specific and an important regulatory step for hPR activity. I have also compared the activity of the mutant Ala400 with the wild type hPR. Surprisingly, the mutant's activity is significantly higher than that of the wild type, implying that regulation of hPR by phosphorylation is complex. Recently, several co-regulators of steroid receptors have been cloned and characterized. I have just begun to study their roles in the RU 486 antagonist/agonist switch. Initial results show that the PKA may potentiate the hPR activity through SRC-1. Whether SRC-1 can mediate the switch is under investigation.
Descriptors : *RECEPTOR SITES(PHYSIOLOGY), *PROGESTERONE, *BREAST CANCER, HUMANS, CELLS, MUTATIONS, YEASTS, CLONES, WILDLIFE, RESIDUES, SENSE ORGANS, SERINE, PHOSPHORYLATION.
Subject Categories : Biochemistry
Medicine and Medical Research
Distribution Statement : APPROVED FOR PUBLIC RELEASE