EXTENDING THE C2 DOMAIN FAMILY - C2S IN PKC-DELTA, PKC-EPSILON, PKC-ETA, PKC-THETA, PHOSPHOLIPASES, GAPS, AND PERFORIN

Various membrane lipid metabolites, generated by phospholipases C and D (PLCs, PLDs), are known to regulate the activities of protein kinase s C (PKCs) and GTP-ase activating proteins (GAPs) in a range of cellul ar processes. Conventional Ca2+-dependent PKCs (alpha, beta I, beta II , and gamma), PLCs, and various GAPs are all known to contain copies o f a phospholipid-binding domain, termed C2 or CalB. Here we recognize that C2 domains are also present in ''new'' Ca2+-independent PKCs (del ta, epsilon, eta, and theta), other kinases, a eukaryotic PLD, the bre akpoint cluster region (BCR) gene product, and two further GAPS. Twent y-two previously unrecognized C2 domain sequences are presented, which include a single copy in the mammalian pore-forming proteins, perfori n.