ABSTRACT
The C2 domains of cPKCs [classical/conventional PKCs (protein kinase Cs)] bind to membranes in a Ca(2+)-dependent manner and thereby act as cellular Ca(2+) effectors. Recent findings have demonstrated that the C2 domain of cPKCs interacts specifically with PtdIns(4,5)P(2) through its polybasic cluster located in the beta3-beta4-strands, this interaction being critical for the membrane localization of these enzymes in living cells. In addition, these C2 domains exhibit higher affinity to bind PtdIns(4,5)P(2) than any other polyphosphate phosphatidylinositols. It has also been shown that the presence of PtdIns(4,5)P(2) in model membranes decreases the Ca(2+) concentration required for classical C2 domains to bind them. Overall, the studies reviewed here suggest a new mechanism of membrane docking by the C2 domains of cPKCs in which the local densities of phosphatidylserine and PtdIns(4,5)P(2) on the inner leaflet of the plasma membrane are sufficient to drive Ca(2+)-activated membrane docking during a physiological Ca(2+) signal.