The C2 domains of classical/conventional PKCs are specific Ptdlns(4,5)P2-sensing domains

The C2 domains of cPKCs [classical/conventional PUS (protein kinase Cs)] bind to membranes in a Ca2+-dependent manner and thereby act as cellular Ca2+ effectors. Recent findings have demonstrated that the C2 domain of cPKCs interacts specifically with Ptdlns(4,S)P-2 through its polybasic cluster located in the beta 3-beta 4-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 Ptdlns(4,5)P-2 than any other polyphosphate phosphatidylinositols. it has also been shown that the presence of Ptdlns(4,5)P-2 in model membranes decreases the Cal(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 Ptdlns(4,5)P-2 on the inner leaflet of the plasma membrane are sufficient to drive Ca2+-activated membrane docking during a physiological Ca2+ signal.