Src-mediated tyrosine phosphorylation of Protein Kinase D2 at focal adhesions regulates cell adhesion

Dependent on their cellular localization, Protein Kinase D (PKD) enzymes regulate different processes including Golgi transport, cell signalingand response to oxidative stress. The localization of PKD within cells is mediated by interaction with different lipid or protein binding partners. With the example of PKD2, we here show that phosphorylation events can also contribute to localization of subcellular pools of this kinase. Specifically, in the present study, we show that tyrosine phosphorylationof PKD2 at residue Y87 defines its localization to the focal adhesionsand leads to activation. This phosphorylation occurs downstream of RhoAsignaling and is mediated via Src. Moreover, mutation of this residue blocks PKD2’s interaction with Focal AdhesionKinase (FAK). The presence and regulation of PKD2 at focal adhesionsidentifies a novel function for this kinase as a modulator of cell adhesion and migration.