THE ROLE OF C2 DOMAINS IN CA2-ACTIVATED AND CA2+ INDEPENDENT PROTEIN-KINASE CS IN APLYSIA()

In the nervous system of the marine mollusk Aplysia there are two prot ein kinase C (PKC) isoforms, the Ca2+-activated PKC Apl I and the Ca2-independent PKC Apl II. PKC Apl I, but not PKC Apl II is activated by a shortterm application of the neurotransmitter serotonin, This may b e explained by the fact that purified PKC Apl II requires a higher mol e percentage of phosphatidylserine to stimulate enzyme activity than d oes PKC Apl I. In order to understand the molecular basis for this dif ference, we have compared the ability of lipids to interact with the p urified kinases and with regulatory domain fusion proteins derived fro m the kinases using a variety of assays including kinase activity, pho rbol dibutyrate binding, and Liposome binding. We found that a C2 doma in fusion protein derived from PKC Apl I binds to lipids constitutivel y, while a C2 domain fusion protein derived from PKC Apl II does not. In contrast, fusion proteins containing the C1 domains of PRC Apl I an d PKC Apl II showed only small differences in lipid interactions. Thus , while the presence of a C2 domain assists lipid-mediated activation of PKC Apl I, it inhibits activation of PKC Apl II.