Protein kinase D1-mediated phosphorylations regulate Vasodilator-stimulated phosphoprotein (VASP) localization and cell migration

Background: Protein kinase D1 (PKD1) regulates actin reorganization processes at the leading edge. Results: PKD1 phosphorylates VASP at two serine residues, Ser-157 and Ser-322. Conclusion: VASP is a substrate for PKD1. Significance: We provide an additional mechanism of how VASP functions can be regulated. Enabled/Vasodilator-stimulated phosphoprotein (Ena/VASP) protein family members link actin dynamics and cellular signaling pathways. VASP localizes to regions of dynamic actin reorganization such as the focal adhesion contacts, the leading edge or filopodia, where it contributes to F-actin filament elongation. Here we identify VASP as a novel substrate for protein kinase D1 (PKD1). We show that PKD1 directly phosphorylates VASP at two serine residues, Ser-157 and Ser-322. These phosphorylations occur in response to RhoA activation and mediate VASP re-localization from focal contacts to the leading edge region. The net result of this PKD1-mediated phosphorylation switch in VASP is increased filopodia formation and length at the leading edge. However, such signaling when persistent induced membrane ruffling and decreased cell motility.