Regulation of protein kinase CK2 catalytic activity by protein kinase C and phospholipase D2.

We have previously demonstrated that phospholipase D2 (PLD2) overexpression antagonizes protein kinase CK2 (CK2) inhibition-mediated cellular senescence. In the current paper, we show the molecular mechanism of CK2 activation by PLD2 and protein kinase C (PKC). Elevated expression and chemical activation of PLD2 increased the catalytic activity of CK2 and PKC in human colon cancer HCT116 and embryonic kidney HEK293 cells, whereas utilization of PLD2 chemical inhibitors and siRNA suppressed this activity. Inhibition of PKC in these cells suppressed PLD2-induced CK2 activation, suggesting that PLD2 enhances CK2 activity through PKC. Overexpression of the PKC isoforms: PKCα, PKCβ, and PKCζ, but not PKCγ, stimulated CK2 activity in the cells. Importantly, purified conventional PKC (cPKC) and atypical PKC (aPKC) enzymes enhanced CK2 activity and phosphorylated serines 194 and 277 within CK2α as well as serine 148 within CK2β. Furthermore, PKC-mediated phosphorylation of these serines on CK2α was crucial for the stimulation of CK2 activity. Taken together, the present results suggest that PLD2 can stimulate CK2 activity through PKC-mediated CK2α phosphorylation.