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首页> 外文期刊>Molecular and Cellular Biology >AIB1 Is a Conduit for Kinase-Mediated Growth Factor Signaling to the Estrogen Receptor
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AIB1 Is a Conduit for Kinase-Mediated Growth Factor Signaling to the Estrogen Receptor

机译：AIB1是激酶介导的生长因子信号转导至雌激素受体的管道。

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Growth factor modulation of estrogen receptor (ER) activity plays an important role in both normal estrogen physiology and the pathogenesis of breast cancer. Growth factors are known to stimulate the ligand-independent activity of ER through the activation of mitogen-activated protein kinase (MAPK) and the direct phosphorylation of ER. We found that the transcriptional activity of AIB1, a ligand-dependent ER coactivator and a gene amplified preferentially in ER-positive breast cancers, is enhanced by MAPK phosphorylation. We demonstrate that AIB1 is a phosphoprotein in vivo and can be phosphorylated in vitro by MAPK. Finally, we observed that MAPK activation of AIB1 stimulates the recruitment of p300 and associated histone acetyltransferase activity. These results suggest that the ability of growth factors to modulate estrogen action may be mediated through MAPK activation of the nuclear receptor coactivator AIB1.
机译：雌激素受体（ER）活性的生长因子调节在正常的雌激素生理和乳腺癌的发病机理中都起着重要作用。已知生长因子通过有丝分裂原激活的蛋白激酶（MAPK）的激活和ER的直接磷酸化来刺激ER的配体非活性。我们发现，MAPK磷酸化增强了AIB1，配体依赖性ER共激活剂和在ER阳性乳腺癌中优先扩增的基因的转录活性。我们证明，AIB1是一种体内的磷蛋白，可以被MAPK体外磷酸化。最后，我们观察到AIB1的MAPK激活刺激了p300的募集以及相关的组蛋白乙酰转移酶活性。这些结果表明，生长因子调节雌激素作用的能力可能是通过核受体共激活因子AIB1的MAPK激活来介导的。

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