Phosphorylation of adducin by protein kinase C promotes cell motility

Protein kinase C (PKC) has been implicated to play a crucial role in cell proliferation, differentiation and apoptosis. In this study, we have investigated the role of PKC in cell motility using Madin-Darby canine kidney cells. Overexpression of PKC promoted membrane protrusions, concomitant with increased cell motility. By contrast, suppression of PKC expression by RNA interference inhibited cell motility. Moreover, a fraction of PKC 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 PKC correlated with increased phosphorylation of adducin at Ser726 in intact cells. In vitro, PKC, but not PKC, directly phosphorylated the Ser726 of adducin. Finally, we demonstrated that overexpression of both adducin and PKC could generate a synergistic effect on promoting cell spreading and cell migration. Our results support a positive role for PKC in cell motility and strongly suggest a link between PKC activity, adducin phosphorylation and cell motility.