Phosphorylation at serine 208 of the 1α,25-dihydroxy Vitamin D3 receptor modulates the interaction with transcriptional coactivators
Phosphorylation at serine 208 of the 1α,25-dihydroxy Vitamin D3 receptor modulates the interaction with transcriptional coactivators
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DOI：
10.1016/j.jsbmb.2006.12.021
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发表时间：
2007-03-01
影响因子：
4.1
通讯作者：
Montecino, Martin
中科院分区：
文献类型：
--
作者：
Arriagada, Gloria;Paredes, Roberto;Montecino, Martin
在配体结合后，1 α 25-二羟基维生素D3受体（VDR）经历构象变化，其允许通过DRIP 205亚基与包括p160/SRC家族成员和多聚体DRIP复合物的共激活蛋白相互作用。酪蛋白激酶II（CKII）在体外和体内在铰链结构域内的丝氨酸208处磷酸化VDR。这种磷酸化不影响VDR结合DNA的能力。但增加其反式激活靶启动子的能力。在这里，我们分析了是否磷酸化的VDR CKII调节VDR的能力，在体外与辅激活剂。我们发现，丝氨酸208突变为天冬氨酸（VDRS 208 D）或通过CKII磷酸化VDR增强了VDR与DRIP 205在1 α，25-二羟基维生素D3存在下的相互作用。我们还发现突变VDRS 208 D既不影响该蛋白结合DNA的能力，也不影响与SRC-1和RXRU相互作用的能力。总之，我们的研究结果表明，在丝氨酸208的VDR磷酸化有助于调节的DRIP复合物的VDR的亲和力，因此可能有一个在体内调节VDR介导的转录增强的作用。(c)2006爱思唯尔有限公司保留所有权利。
Upon ligand bindina the 1 alpha.25-dihydroxy Vitamin D3 receptor (VDR) undergoes a conformational change that allows interaction with coactivator proteins including p160/SRC family members and the multimeric DRIP complex through the DRIP205 subunit. Casein kinase II (CKII) phosphorylates VDR both in vitro and in vivo at serine 208 within the hinge domain. This phosphorylation does not affect the ability of VDR to bind DNA. but increases its ability to transactivate target promoters. Here, we have analyzed whether phosphorylation of VDR by CKII modulates the ability of VDR to interact with coactivators in vitro. We find that both mutation of serine 208 to aspartic acid (VDRS208D) or phosphorylation of VDR by CKII enhance the interaction of VDR with DRIP205 in the presence of 1 alpha,25-dihydroxy Vitamin D3. We also find that the mutation VDRS208D neither affects the ability of this protein to bind DNA nor to interact with SRC-1 and RXRU. Together, our results indicate that phosphorylation of VDR at serine 208 contributes to modulate the affinity of VDR for the DRIP complex and therefore may have a role in vivo regulating VDR-mediated transcriptional enhancement. (c) 2006 Elsevier Ltd. All rights reserved.