Serine 27, a human Retinoid X Receptor α residue, phosphorylated by protein kinase A is essential for CyclicAMP-mediated downregulation of RXRα function
Serine 27, a human Retinoid X Receptor α residue, phosphorylated by protein kinase A is essential for CyclicAMP-mediated downregulation of RXRα function
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DOI：
10.1006/bbrc.2000.4043
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发表时间：
2000-12-29
影响因子：
3.1
通讯作者：
Rangarajan, PN
中科院分区：
文献类型：
--
作者：
Harish, S;Ashok, MS;Rangarajan, PN
维甲酸X受体α（RXR α）是类固醇-甲状腺激素受体超家族的成员，在体外被蛋白激酶A（PKA）磷酸化，并且这种磷酸化在PKA抑制肽的存在下被抑制。对RXR α的各种缺失突变体的分析表明，氨基末端A/B结构域是PKA磷酸化的靶标。丝氨酸残基27突变为丙氨酸的RXR α突变体不再被PKA磷酸化。COS细胞中的体内转染实验表明，cyclicAMP抑制视黄酸介导的RXR α的转录激活，这种抑制是由丝氨酸27介导的。这些结果表明，RXR α的丝氨酸27是PKA体外磷酸化的独特靶标，并且在RXR α和cyclicAMP信号通路之间的串扰中具有重要作用。(C)北京大学出版社.
Retinoid X Receptor alpha (RXR alpha), a member of the steroid-thyroid hormone receptor super family, is phosphorylated in vitro by protein kinase A (PKA) and this phosphorylation is inhibited in presence of PKA inhibitory peptide. Analysis of various deletion mutants of RXR alpha indicate that the amino-terminal A/B domain is the target for PKA phosphorylation. An RXR alpha mutant in which serine residue 27 is mutated to alanine is no longer phosphorylated by PKA. In vivo transfection experiments in COS cells indicate that cyclicAMP represses retinoic acid-mediated transcriptional activation of RXR alpha and this repression is mediated by serine 27. These results indicate that serine 27 of RXR alpha is an unique target for phosphorylation by PKA in vitro and it has an important role in the crosstalk between RXR alpha and cyclicAMP signalling pathways. (C) 2000 Academic Press.