REGULATION OF PROGESTERONE RECEPTOR-MEDIATED TRANSCRIPTION BY PHOSPHORYLATION

REGULATION OF PROGESTERONE RECEPTOR-MEDIATED TRANSCRIPTION BY PHOSPHORYLATION
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DOI:
10.1126/science.2176746
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发表时间:
1990-12-21
期刊:
影响因子:
56.9
通讯作者:
OMALLEY, BW
OMALLEY, BW
中科院分区:
综合性期刊1区
文献类型:
--
作者:
DENNER, LA;WEIGEL, NL;OMALLEY, BW

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鸡输卵管中的孕酮受体(PR)是一种磷蛋白,在孕酮存在下调节基因转录。用孕酮在体内处理刺激孕酮受体的磷酸化。与瞬时转染试验,目前的工作已经测试是否磷酸化参与PR介导的转录的调节。8-溴环腺苷酸(8-Br cAMP),cAMP依赖性蛋白激酶[蛋白激酶A(PKA)]的刺激剂,模拟孕酮依赖性,受体介导的转录在孕酮的情况下的治疗。PKA的抑制阻断了激素的作用。用蛋白磷酸酶1和2A的抑制剂冈田酸处理,以类似于孕酮的方式刺激转录。这些观察结果表明,PR或转录复合物中的其他蛋白质的磷酸化可以调节PR介导的体内转录。
The progesterone receptor (PR) in the chicken oviduct is a phosphoprotein that regulates gene transcription in the presence of progesterone. Treatment with progesterone in vivo stimulates phosphorylation of the progesterone receptor. With transient transfection assays, the present work has tested whether phosphorylation participates in the regulation of PR-mediated transcription. Treatment with 8-bromo-cyclic adenosine monophosphate (8-Br cAMP), a stimulator of cAMP-dependent protein kinase [protein kinase A (PKA)], mimicked progesterone-dependent, receptor-mediated transcription in the absence of progesterone. Inhibition of PKA blocked hormone action. Treatment with okadaic acid, an inhibitor of protein phosphatases 1 and 2A, stimulated transcription in a manner similar to that of progesterone. These observations suggest that phosphorylation of the PR or other proteins in the transcription complex can modulate PR-mediated transcription in vivo.