Androgen receptor specifically interacts with a novel p21-activated kinase, PAK6
Androgen receptor specifically interacts with a novel p21-activated kinase, PAK6
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DOI：
10.1074/jbc.m010311200
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发表时间：
2001-05-04
影响因子：
4.8
通讯作者：
Sun, Z
中科院分区：
文献类型：
--
作者：
Yang, F;Lio, XY;Sun, Z
雄激素受体(AR)是一种激素依赖的转录因子，在男性性别分化和发育中发挥重要作用。类固醇激素受体(如雄激素受体)的转录激活是通过与辅因子的相互作用来调节的。我们最近发现了一种新的AR相互作用蛋白，暂时命名为PAK6，它与p21激活的激酶(PAKs)具有高度的序列相似性。PAK6是一个75 kDa的蛋白质，含有一个可能的氨基末端的CDC42/RAC相互作用结合基序和一个羧基末端的激酶结构域。在体内和体外，进一步证实了AR和PAK6之间存在结构域特异性和配体依赖性的相互作用。Northern印迹分析表明，PAK6在睾丸和前列腺组织中高表达。最重要的是，免疫荧光研究表明，在雄激素作用下，PAK6与AR共转位到细胞核内，瞬时转染实验表明，PAK6特异性地抑制AR介导的转录，本报告发现了PAK同源蛋白的一个新功能，并提出了一种潜在的独特机制，通过该机制，其他信号转导途径可能与AR途径相互作用，调节正常和恶性前列腺细胞的AR功能。
The androgen receptor (AR) is a hormone-dependent transcription factor that plays important roles in male sexual differentiation and development. Transcription activation by steroid hormone receptors, such as the androgen receptor, is mediated through interaction with cofactors. We recently identified a novel AR-interacting protein, provisionally termed PAK6, that shares a high degree of sequence similarity with p21-activated kinases (PAKs). PAK6 is a 75-kDa protein that contains a putative amino-terminal Cdc42/Rac interactive binding motif and a carboxyl-terminal kinase domain. A domain-specific and ligand dependent interaction between AR and PAK6 was further confirmed in vivo and in vitro. Northern blot analysis revealed that PAK6 is highly expressed in testis and prostate tissues. Most importantly, immunofluorescence studies showed that PAK6 cotranslocates into the nucleus with AR in response to androgen, Transient transfection experiments showed that PAK6 specifically repressed AR-mediated transcription, This report identifies a novel function for a PAK-homologous protein and suggests a potential unique mechanism by which other signal transduction pathways may cross-talk with AR pathways to regulate AR function in normal and malignant prostate cells.