Chen Cuixia, Shang Xin, Cui Lingling, Xu Ting, Luo Jixian, Ba Xueqing, Zeng Xianlu
Institute of Genetics and Cytology, Northeast Normal University, Changchun 130024, People's Republic of China.
Hum Immunol. 2008 Aug;69(8):501-9. doi: 10.1016/j.humimm.2008.06.005. Epub 2008 Jul 9.
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.
L-选择素是一种细胞粘附分子，在介导白细胞沿内皮细胞的初始捕获和随后的滚动以及白细胞激活的信号转导中均发挥重要作用。在我们之前的研究中，我们报道L-选择素连接可增加巨噬细胞集落刺激因子（CSF）-1基因转录，其中c-Abl作为关键的胞质激酶发挥作用。在此，我们研究了核c-Abl激酶在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L-选择素连接后c-Abl激酶会募集到细胞核，并且核c-Abl激酶可磷酸化c-Jun并调节激活蛋白（AP）-1活性。此外，活化的c-Abl激酶与AP-1相互作用并在CSF-1启动子区域形成复合物，以调节L-选择素连接激活的细胞中的CSF-1基因转录。这些结果表明，核c-Abl激酶可通过在L-选择素连接诱导的信号事件中调节AP-1活性来激活CSF-1基因转录。
