Rac1 plays a crucial role in MCP-1-induced monocyte adhesion and migration.

[Display omitted] • MCP1- induced iPLA 2 activation regulates downstream activation of Rac1. • Rac1 directly interacts with its upstream regulator iPLA 2 and downstream Pyk2. • Rac1 regulates monocyte adhesion and migration via activation of Pyk2 and p38MAPK. • MCP1-induced activated Rac1 regulates extracellular vimentin secretion in monocytes. • Rac1 is a potential therapeutic target for the resolution of inflammation. Monocyte migration is an important process in inflammation and atherogenesis. Identification of the key signalling pathways that regulate monocyte migration can provide prospective targets for prophylactic treatments in inflammatory diseases. Previous research showed that the focal adhesion kinase Pyk2, Src kinase and MAP kinases play an important role in MCP-1-induced monocyte migration. In this study, we demonstrate that MCP-1 induces iPLA 2 activity, which is regulated by PKCβ and affects downstream activation of Rac1 and Pyk2. Rac1 interacts directly with iPLA 2 and Pyk2, and plays a crucial role in MCP-1-mediated monocyte migration by modulating downstream Pyk2 and p38 MAPK activation. Furthermore, Rac1 is necessary for cell spreading and F-actin polymerization during monocyte adhesion to fibronectin. Finally, we provide evidence that Rac1 controls the secretion of inflammatory mediator vimentin from MCP-1-stimulated monocytes. Altogether, this study demonstrates that the PKCβ/iPLA 2 /Rac1/Pyk2/p38 MAPK signalling cascade is essential for MCP-1-induced monocyte adhesion and migration. [ABSTRACT FROM AUTHOR]