Phosphorylation of the nuclear receptor SF-1 modulates cofactor recruitment: Integration of hormone signaling in reproduction and stress
Phosphorylation of the nuclear receptor SF-1 modulates cofactor recruitment: Integration of hormone signaling in reproduction and stress
复制标题
DOI：
10.1016/s1097-2765(00)80480-3
复制
发表时间：
1999-04-01
期刊：
影响因子：
16
通讯作者：
Ingraham, HA
中科院分区：
文献类型：
--
作者：
Hammer, GD;Krylova, I;Ingraham, HA
类固醇生成因子1（steroidogenicfactor 1，SF-1）是一种孤儿核受体，在脊椎动物内分泌系统中作为多种激素诱导基因的重要调节因子。SF-1配体的明显缺乏促使推测该受体受涉及信号转导途径的替代机制调节。在这里，我们表明，最大SF-1介导的转录和相互作用与一般核受体辅因子依赖于磷酸化的一个单一的丝氨酸残基（Ser-203）位于一个主要的激活结构域（AF-1）的蛋白质。此外，磷酸化依赖性SF-1激活可能是由丝裂原活化蛋白激酶（MAPK）信号通路介导的。我们认为，SF-1的这种单一修饰和随后的核受体辅因子的募集将细胞外信号与类固醇和肽类激素合成偶联，从而维持应激和生殖中的动态稳态反应。
Steroidogenic factor 1 (SF-1) is an orphan nuclear receptor that serves as an essential regulator of many hormone-induced genes in the vertebrate endocrine system. The apparent absence of a SF-1 ligand prompted speculation that this receptor is regulated by alternative mechanisms involving signal transduction pathways. Here we show that maximal SF-1-mediated transcription and interaction with general nuclear receptor cofactors depends on phosphorylation of a single serine residue (Ser-203) located in a major activation domain (AF-1) of the protein. Moreover, phosphorylation-dependent SF-1 activation is likely mediated by the mitogen-activated protein kinase (MAPK) signaling pathway. We propose that this single modification of SF-1 and the subsequent recruitment of nuclear receptor cofactors couple extracellular signals to steroid and peptide hormone synthesis, thereby maintaining dynamic homeostatic responses in stress and reproduction.