Beschreibung:
<jats:p>Monocyte chemotactic protein 1 (MCP1) stimulates vascular smooth muscle cell (VSMC) migration in vascular wall remodeling. However, the mechanisms underlying MCP1‐induced VSMC migration have not been understood. Here we have identified the signaling pathway associated with MCP1‐induced human aortic smooth muscle cell (HASMC) migration. MCP1, a G protein‐coupled receptor agonist, activated phosphorylation of cortactin on S405 and S418 residues in a time‐dependent manner and inhibition of its phosphorylation attenuated MCP1‐induced HASMC G‐actin polymerization, F‐actin stress fiber formation and migration. Cortactin phosphorylation on S405/S418 was found to be critical for its interaction with WAVE2, a member of the WASP family of cytoskeletal regulatory proteins required for cell migration. In addition, the MCP1‐induced cortactin phosphorylation was dependent on PLCβ3‐mediated PKCδ activation and siRNA‐mediated down regulation of either one of these molecules prevented cortactin interaction with WAVE2 affecting G‐actin polymerization, F‐actin stress fiber formation and HASMC migration. At the upstream, MCP1 activated CCR2 and Gαq/11 in a time‐dependent manner and down regulation of their levels attenuated MCP1‐induced PLCβ3 and PKCδ activation, cortactin phosphorylation, cortactin‐WAVE2 interaction, G‐actin polymerization, F‐actin stress fiber formation and HASMC migration. Together, these findings demonstrate that phosphorylation of cortactin on S405 and S418 residues is required for its interaction with WAVE2 in MCP1‐induced cytoskeleton remodeling facilitating HASMC migration.</jats:p><jats:p><jats:bold>Support or Funding Information</jats:bold></jats:p><jats:p>This work was supported by NIH grants HL069908 and HL103575 to GNR</jats:p>