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.