Thyrotropin-releasing Hormone (TRH) specific interaction between amino terminus of P-Lim and CREB binding protein (CBP)
Thyrotropin-releasing Hormone (TRH) specific interaction between amino terminus of P-Lim and CREB binding protein (CBP)
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DOI：
10.1016/j.mce.2004.10.005
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发表时间：
2005-01-14
影响因子：
4.1
通讯作者：
Mori, M
中科院分区：
文献类型：
--
作者：
Hashimoto, K;Yamada, M;Mori, M
P-Lim（Lhx 3a）是小鼠垂体发育和运动神经元特化所必需的LIM同源域转录因子。Lhx 3基因编码两种亚型，其氨基（N）末端不同。Lhx 3a和3b。糖蛋白激素α亚基（α-GSU）基因启动子上的P-Lim DNA结合位点在哺乳动物中是保守的。正如我们先前报道的，P-Lim通过结合CREB结合蛋白（CBP）在介导促甲状腺激素释放激素（TRH）信号传导中起着关键作用。Hem，我们证明了P-Lim（Lhx 3a）而不是Lhx 3b可以介导TRH信号传导并与CBP结合。而且。TRH通过P-Lim的N-末端特异性诱导P-Lim-CBP结合。我们还发现，蛋白激酶C（PKC）磷酸化位点内的N-末端的P-Lim是负责P-Lim-CBP的结合，这表明TRH信号通路磷酸化P-Lim。这些研究阐明了TRH刺激α-GSU基因表达的分子机制。(C)2004爱思唯尔爱尔兰有限公司保留所有权利。
P-Lim (Lhx3a) is a LIM homeodomain transcription factor essential for pituitary development and motor neuron specification in mice. The Lhx3 gene encodes two isoforms, which differ in their amino (N) termini. Lhx3a and 3b. The P-Lim DNA binding site on the glycoprotein hormone alpha subunit (alpha-GSU) gene promoter is conserved in mammals. P-Lim plays a pivotal role in mediating thyrotropin-releasing hormone (TRH) signaling by binding CREB binding protein (CBP), as we have reported previously. Hem, we demonstrate that P-Lim (Lhx3a) but not Lhx3b can mediate TRH signaling and bind to CBP. Moreover. TRH specifically induces P-Lim-CBP binding through the N-termini of P-Lim. We also found that the protein kinase C (PKC) phosphorylation site within the N-terminus of P-Lim is responsible for the P-Lim-CBP binding suggesting that the TRH signaling pathway phosphorylates P-Lim. These studies have elucidated the molecular mechanism by which TRH Stimulates a-GSU gene expression. (C) 2004 Elsevier Ireland Ltd. All rights reserved.