L-selectin ligation-induced CSF-1 gene transcription is regulated by AP-1 in a c-Abl kinase-dependent manner
L-selectin ligation-induced CSF-1 gene transcription is regulated by AP-1 in a c-Abl kinase-dependent manner
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DOI：
10.1016/j.humimm.2008.06.005
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发表时间：
2008-08-01
期刊：
影响因子：
2.7
通讯作者：
Zeng, Xianlu
中科院分区：
文献类型：
--
作者：
Chen, Cuixia;Shang, Xin;Zeng, Xianlu
L-选择素是一种细胞粘附分子，在介导白细胞沿着内皮细胞的初始捕获和随后的滚动以及白细胞活化的信号转导中起重要作用。在我们以前的研究中，我们报道了L-选择素连接可以增加巨噬细胞集落刺激因子（CSF）-1基因的转录，其中c-Abl作为一个重要的胞浆激酶。在这里，我们研究了核c-Abl激酶在由L-选择素连接触发的CSF-1基因转录事件中的功能。我们确定c-Abl激酶在L-选择素连接后募集到细胞核，并且细胞核c-Abl激酶可以磷酸化c-Jun并调节激活蛋白（AP）-1活性。此外，激活的c-Abl激酶与AP-1相互作用，并在CSF-1启动子区形成复合物，以调节L-选择素连接激活的细胞中CSF-1基因的转录。这些结果表明，核c-Abl激酶可以通过调节L-选择素连接诱导的信号事件中的AP-1活性来激活CSF-1基因的转录。(C)2008年由Elsevier Inc.出版All rights reserved.
L-selectin is a cell adhesion molecule that plays an important role both in mediating the initial capture and subsequent rolling of leukocytes along the endothelial cells and in the signal transduction for leukocyte activation. In our previous studies, we reported that L-selectin ligation could increase macrophage colony-stimulating factor (CSF)-1 gene transcription, in which c-Abl acts as a crucial cytoplasmic kinase. Here we investigated the function of the nuclear c-Abl kinase in the CSF-1 gene transcriptional events triggered by L-selectin ligation. We determined that c-Abl kinase recruits to the nucleus following L-selectin ligation, and the nuclear c-Abl kinase can phosphorylate c-Jun and regulate activator protein (AP)-1 activity. Furthermore, the activated c-Abl kinase interacts with AP-1 and forms a complex in the CSF-1 promoter region to regulate CSF-1 gene transcription in the L-selectin ligation-activated cells. These results indicate that nuclear c-Abl kinase can activate CSF-1 gene transcription by regulating AP-1 activity in the signaling events induced by L-selectin ligation. (C) 2008 Published by Elsevier Inc. All rights reserved.