{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T21:31:59Z","timestamp":1792704719477,"version":"4.5.0"},"reference-count":74,"publisher":"American Society for Cell Biology (ASCB)","issue":"25","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["MBoC"],"published-print":{"date-parts":[[2015,12,15]]},"abstract":"<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 identify the signaling pathway associated with MCP1-induced human aortic smooth muscle cell (HASMC) migration. MCP1, a G protein\u2013coupled receptor agonist, activates phosphorylation of cortactin on S405 and S418 residues in a time-dependent manner, and inhibition of its phosphorylation attenuates MCP1-induced HASMC G-actin polymerization, F-actin stress fiber formation, and migration. Cortactin phosphorylation on S405\/S418 is 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 is dependent on PLC\u03b23-mediated PKC\u03b4 activation, and siRNA-mediated down-regulation of either of these molecules prevents cortactin interaction with WAVE2, affecting G-actin polymerization, F-actin stress fiber formation, and HASMC migration. Upstream, MCP1 activates CCR2 and G\u03b1q\/11 in a time-dependent manner, and down-regulation of their levels attenuates MCP1-induced PLC\u03b23 and PKC\u03b4 activation, cortactin phosphorylation, cortactin\u2013WAVE2 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>","DOI":"10.1091\/mbc.e15-08-0570","type":"journal-article","created":{"date-parts":[[2015,10,22]],"date-time":"2015-10-22T02:59:18Z","timestamp":1445482758000},"page":"4589-4606","source":"Crossref","is-referenced-by-count":23,"title":["PLC\u03b23 mediates cortactin interaction with WAVE2 in MCP1-induced actin polymerization and cell migration"],"prefix":"10.1091","volume":"26","author":[{"given":"Jagadeesh","family":"Janjanam","sequence":"first","affiliation":[{"name":"Department of Physiology, University of Tennessee Health Science Center, Memphis, TN 38163"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giri Kumar","family":"Chandaka","sequence":"additional","affiliation":[{"name":"Department of Physiology, University of Tennessee Health Science 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