The migration of vascular smooth muscle cells (VSMCs) is a key event in the pathogenesis of many vascular disorders. We have previously shown that VSMC migration is suppressed in growth-arrested VSMCs due the failure of these cells to activate calcium/calmodulin-dependent protein kinase (CamKinase) II in response to the chemoattractant, platelet-derived growth factor (PDGF). This was convincingly demonstrated by overexpressing constitutively activated Cam Kinase II in VSMCs and showing these VSMCs were capable of migrating toward PDGF even when the cells had been growth-arrested. We have recently demonstrated that autocrine stimulation of VSMCs by basic fibroblast growth factor (bFGF) is required for VSMCs migration and Cam Kinase II activation. bFGF's effect on migration is likely due its role in enabling PDGF to activate CamKII since 1) bFGF antibodies block activation of CamKII in response to PDGF, while the migration of VSMCs expressing constitutively active CamKII is not affected by these antibodies; and 2) the ability of exogenous bFGF to stimulate migration in growth-arrested cells is blocked by CamKII inhibition. In vivo, the ability of VSMCs to respond to PDGF and migrate is also controlled by interactions between VSMCs and the extracellular matrix (ECM). Our recent studies have shown that occupancy of avb3 integrin, which has been shown by other members in the laboratory to upregulated in vivo in response to vessel injury, is required for VSMC migration in vitro and for the activation of Cam Kinase II in response to PDGF. The migration of stably transfected VSMCs or VSMCs infected with a recombinant adenovirus expressing constitutively activatated Cam Kinase II is unaffected by reagents that block avb3-ECM interactions. These results demonstrate that multiple intracellular signaling pathways triggered by chemoattractant recognition and integrin-ECM interactions are essential for migration and define one possible mechanistic link between integrin-mediated events and chemoattractant/growth factor signaling.