Protein Kinase C: Plasma Membrane to Nucleus
It seems well founded that one of the major pathways of transmembrane signalling is mediated via activation of calcium-phospholipid dependent protein kinase known as protein kinase C (1). Ever since its discovery by Nishizuka in 1979, the enzyme has been implicated in a range of cellular response including that of growth and proliferation. The mechanism of action of protein kinase C seems to require association of the enzyme with plasma membrane to prime the activity. In this scenario diacylglycerol acts as the endogenous kinase C activator. Diacylglycerol is one of the breakdown products of phosphatidylinositol (2) catalyzed by specific phospholipase C activated by the binding of growth modulators to their respective receptors located on the plasma membrane. The other hydrolytic product of the inositol cycle is 1,4,5 inositol trisphosphate which releases calcium from endoplasmic reticulum. Physiological calcium levels may be modulated ranging from 0.1–1.0 µM, by a variety of stimuli. In fact, the elevated calcium levels do not lead to protein kinase C activation but elicit rapid and reversible association of the enzyme with the membrane. These calcium levels increase the apparent affinity of phorbol esters (TPA) to whole cells.
KeywordsPhorbol Ester Inositol Trisphosphate Cofactor Requirement Calcium Optimum Elevated Calcium Level
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