Activation of protein kinase C by short chain phospholipid micelles

PKC (80 kDa) can be cleaved by limited proteolysis into distinct catalytic (50 kDa) and regulatory (32-35 kDa) fragments. After cleavage, the catalytic fragment is active in the absence of Ca2+, phospholipid, or DAG while the regulatory fragment is found associated with phospholipid and continues to bind phorbol esters in a Ca2(+)- and PS-dependent manner (28, 29). In the holoenzyme, the association of the regulatory domain with the membrane may be important to release the catalytic domain from inhibition by the regulatory domain. We have presented evidence indicating that effective membrane binding occurs through interaction with the hydrophobic and/or interfacial regions of the bilayer, and does not result from binding to individual phospholipids. In vivo and in vitro studies suggest that the binding event is carefully regulated. An important function of Ca2+ may be to modify the local structure of the membrane, and thus affect the ability of PKC to associate with it. For at least one of the isozymes, however, Ca2+ may also play an additional role at a site distant from the membrane, suggesting the possibility that the isozymes may be differentially regulated.