Protein Kinase C and Lipid Signalling for Cellular Regulation
It is well documented that protein kinase C (PKC) is activated by increased levels of diacylglycerol (DG) in the membrane that is produced as a result of hydrolysis of inositol phospholipids (PI) by signal-induced activation of phospholipase C (PLC) (Nishizuka, 1992). Recently, attention has been paid to the hydrolysis of other phospholipids, particularly phosphatidylcholine (PC). This reaction produces DG at a relatively later phase in cellular responses, and possible involvement of phospholipase D (PLD) in PKC activation has been postulated (see for reviews: Billah & Anthes, 1990; Exton, 1990; Cockcroft, 1992). Sustained activation of PKC is a prerequisite essential for long-term responses such as cell proliferation and differentiation. In addition, phospholipase A2 (PLA2) is activated by most of the signals which induce PI hydrolysis. Arachidonic acid regulates many physiological processes after its conversion to various eicosanoids, but products of PC hydrolysis catalyzed by PLA2 potentiate PKC activation, thereby contributing to the signal transduction (Asaoka et al., 1992a). However, the biochemical mechanism of activation of phospholipases D and A2 remains largely unknown.
KeywordsPhosphatidic Acid Phorbol Ester Fatty Acid Release Cholesterol Sulfate PLA2 Enzyme
Unable to display preview. Download preview PDF.
- Akimoto K, Mizuno K, Osada S, Hirai S, Tanuma S, Suzuki K and Ohno S (1994) A new member of the third class in the protein kinase C family, PKCλ, expressed dominantly in an undifferentiated mouse embryonal cartinoma cell line and also in many tissues and cells. J. Biol. Chem. 269: in pressGoogle Scholar
- Cockcroft S (1992) G-protein-regulated phospholipases D, D and A2-mediated signalling in neutrophils. Biochim. Biochys. Acta 1113: 135–160Google Scholar
- Ikuta T, Chida K, Tajima 0, Matsuura Y, Iwamori M, Ueda Y, Mizuno K, Ohno S and Kuroki T (1994) Cholesterol sulfate, a novel activator for the η isoform of protein kinase C. Cell Growth & Differentiation: in pressGoogle Scholar
- Kusner DJ, Schomisch SJ and Dubyak GR (1993) ATP-induced potentiation of G-protein-dependent phospholipase D activity in cell-free system from U937 promonocytic leukocytes. J. Biol. Chem. 267: 19973–19982Google Scholar
- Nishida E and Gotoh Y (1993) The MAP kinase cascade is essential for diverse signal transduction pathways. Trends Biochem. Sci. 18: 128–131Google Scholar