Platelet-derived growth factor (PDGF) potently induces migration of vascular smooth muscle cells (VSMC); however, molecular mechanism underlying this phenomenon remains unclear. The migration of rat aorta-derived synthetic VSMCs, A7r5, in response to PDGF was potently inhibited by a CaV1.2 channel inhibitor, nifedipine, and a Src family tyrosine kinase inhibitor, bosutinib, in a less-than-additive manner. In contractile VSMCs, the C-terminus of CaV1.2 is proteolytically cleaved into proximal and distal C-termini (PCT and DCT, respectively). Clipped DCT is noncovalently reassociated with PCT to autoinhibit the channel activity. Conversely, in synthetic A7r5 cells, full-length CaV1.2 (CaV1.2FL) is expressed much more abundantly than truncated CaV1.2. In a heterologous expression system, c-Src was bound to, phosphorylated Tyr1709 and Tyr1758 in PCT and activated CaV1.2 channels composed of CaV1.2FL significantly more efficiently than CaV1.2 (CaV1.2delta1763) or CaV1.2delta1763 plus clipped DCT. Therefore, in atherosclerotic lesions, phenotypic switching of VSMCs may facilitate pro-migratory effects of PDGF on VSMCs by suppressing posttranslational CaV1.2 modifications.