Phosphorylation of adducin by protein kinase Cδ promotes cell motility

Protein kinase Cδ (PKCδ) has been implicated to play a crucial role in cell proliferation, differentiation and apoptosis. In this study, we have investigated the role of PKCδ in cell motility using Madin-Darby canine kidney cells. Overexpression of PKCδ promoted membrane protrusions, concomitant with increased cell motility. By contrast, suppression of PKCδ expression by RNA interference inhibited cell motility. Moreover, a fraction of PKCδ was detected at the edge of membrane protrusions in which it colocalized with adducin, a membrane skeletal protein whose phosphorylation state is important for remodeling of the cortical actin cytoskeleton. Elevated expression of PKCδ correlated with increased phosphorylation of adducin at Ser726 in intact cells. In vitro, PKCδ, but not PKCα, directly phosphorylated the Ser726 of adducin. Finatly, we demonstrated that overexpression of both adducin and PKCδ could generate a synergistic effect on promoting cell spreading and cell migration. Our results support a positive role for PKCδ in cell motility and strongly suggest a link between PKCδ activity, adducin phosphorylation and cell motility.