合成类视黄醇Am80通过诱导血管平滑肌细胞中由PI3K/Akt信号介导的KLF5去磷酸化，抑制KLF5与RARα的相互作用。

Synthetic retinoid Am80 inhibits interaction of KLF5 with RAR alpha through inducing KLF5 dephosphorylation mediated by the PI3K/Akt signaling in vascular smooth muscle cells.

作者信息

Zhang Xin-hua, Zheng Bin, Han Mei, Miao Sui-bing, Wen Jin-kun

机构信息

Department of Biochemistry and Molecular Biology, Hebei Medical University, No. 361, Zhongshan East Road, Shijiazhuang 050017, China.

出版信息

FEBS Lett. 2009 Apr 17;583(8):1231-6. doi: 10.1016/j.febslet.2009.03.016. Epub 2009 Mar 16.

DOI:10.1016/j.febslet.2009.03.016

Abstract

Krüppel-like factor 5 (KLF5) is known to physically interact with retinoic acid receptor-alpha (RAR alpha). Here, we show that Am80 inhibited the interaction between KLF5 and RAR alpha and this inhibitory effect was accompanied by the dephosphorylation of KLF5 in VSMCs. Treating VSMCs with LY294002, the PI3K/Akt inhibitor, abrogated Am80-induced KLF5 dephosphorylation and reversed Am80-induced suppression of interaction between KLF5 and RAR alpha, whereas treating vascular smooth muscle cells (VSMCs) with SB203580, the p38 kinase inhibitor, attenuated the interaction between KLF5 and RAR alpha. Constitutively active p38 kinase MKK6b infection prevented the KLF5 dephosphorylation induced by Am80. In conclusion, Am80 induces KLF5 dephosphorylation by activating PI3K/Akt signaling, and inhibits KLF5 phosphorylation by blocking p38 signaling, subsequently leading to the suppression of interaction of KLF5 with RAR alpha.

摘要

已知Krüppel样因子5（KLF5）与视黄酸受体α（RARα）存在物理相互作用。在此，我们发现Am80抑制了KLF5与RARα之间的相互作用，并且这种抑制作用伴随着血管平滑肌细胞（VSMC）中KLF5的去磷酸化。用PI3K/Akt抑制剂LY294002处理VSMC，消除了Am80诱导的KLF5去磷酸化，并逆转了Am80诱导的KLF5与RARα之间相互作用的抑制，而用p38激酶抑制剂SB203580处理血管平滑肌细胞（VSMC），则减弱了KLF5与RARα之间的相互作用。组成型活性p38激酶MKK6b感染可阻止Am80诱导的KLF5去磷酸化。总之，Am80通过激活PI3K/Akt信号通路诱导KLF5去磷酸化，并通过阻断p38信号通路抑制KLF5磷酸化，随后导致KLF5与RARα相互作用的抑制。