|Budget Amount *help
¥330,000,000 (Direct Cost: ¥330,000,000)
Fiscal Year 1992: ¥70,000,000 (Direct Cost: ¥70,000,000)
Fiscal Year 1991: ¥70,000,000 (Direct Cost: ¥70,000,000)
Fiscal Year 1990: ¥70,000,000 (Direct Cost: ¥70,000,000)
Fiscal Year 1989: ¥120,000,000 (Direct Cost: ¥120,000,000)
Protein kinase C(PKC)family plays crucial roles in signal transduction for control of a variety of physiological processes. The purpose of the present study was to clarify the structures,mechanism of activation as well as the functions of the PKC family in cellular signal transduction. Molecular cloning and biochemical studies clarified the existence of various subspecies of PKC such as alpha,betaI,betaII,gamma,delta,epsilon, and zeta. The enzymological properties,mode of activation,and localization of these subspecies were shown to be different one another,suggesting that each subspecies has specific roles. Although the hydrolysis of inositol phospholipids was initially thought to be the only mechanism leading to the activation of PKC,it was found that the products of phospholipase A2 reaction may regulate PKC pathway. Firstly,unsaturated fatty acids were shown to enhance the PKC activity in the presence of diacylglycerol. The synergistic action of diacylglycerol and unsaturated fatty acids seems to suggest that signal- induced release of unsaturated fatty acids from several phospholipids may take part in enhancing the activation of PKC to play a key role in the development of long-term potentiation. Secondly,the other product of the phospholipase A2 reaction, lysophosphatidylcholine,potentiates the PKC activity,and thereby enhances greatly T-lymphocyte proliferation and HL-60 dell defferentiation. Thus,the activation of PKC seems to be an integral art of the signal-induced degradation cascade of various membrane phospholipids,that is catalyzed by phospholipases C,A2,and D. Analysis of interactions among various pathways to activate these phospholipases may provide clue to understand further the mechanism of cellular responses under physiological and pathological conditions.