Tremblay A, Tremblay G B, Labrie F, Giguère V
Molecular Oncology Group, McGill University Health Centre, Montréal, Québec, Canada.
Mol Cell. 1999 Apr;3(4):513-9. doi: 10.1016/s1097-2765(00)80479-7.
The estrogen receptors (ERs) alpha and beta possess a constitutive N-terminal activation function (AF-1) whose activity can be modulated by kinase signalling pathways. We demonstrate here that phosphorylation of AF-1 by MAP kinase (MAPK) leads to the recruitment of steroid receptor coactivator-1 (SRC-1) by ER beta in vitro. Enhancement of the interaction between SRC-1 and ER beta AF-1 is also observed in vivo in cells either treated with EGF or expressing activated Ras. Two serine residues in ER beta AF-1, of which one is contained within a motif present in other steroid receptors, are critical for physical interaction with SRC-1 and transcriptional activation. Our results establish a role for nuclear receptor phosphorylation in the recruitment of SRC-1 and provide a molecular basis for ligand-independent activation by ER beta via the MAPK pathway.
雌激素受体（ERs）α和β具有组成型的N端激活功能（AF-1），其活性可被激酶信号通路调节。我们在此证明，丝裂原活化蛋白激酶（MAPK）对AF-1的磷酸化作用在体外导致ERβ募集类固醇受体辅激活因子-1（SRC-1）。在用表皮生长因子（EGF）处理或表达活化Ras的细胞中，体内也观察到SRC-1与ERβ AF-1之间相互作用的增强。ERβ AF-1中的两个丝氨酸残基对与SRC-1的物理相互作用和转录激活至关重要，其中一个丝氨酸残基位于其他类固醇受体中存在的一个基序内。我们的结果确立了核受体磷酸化在募集SRC-1中的作用，并为ERβ通过MAPK途径进行非配体依赖性激活提供了分子基础。
