Protein Kinase C and Smooth Muscle Contraction

• Protein kinase C (PKC) is a family of phospholipiddependent Ca 2+ /diacylglycerol-stimulated enzymes. It is an ubiquitous protein that plays a multifunctional role in the transduction of extracellular signals activating the phospholipid turnover and generating diacylglycerol (DAG). DAG can be produced from the hydrolysis of phospatidylinositol-1,4-bisphosphate, phosphatidylcholine, or sphingomyelin by respective phospholipases. PKC is also the major intracellular receptor for phorbol esters, potent tumor promoters, which may replace DAG for its activity. To date, 12 different PKC isoforms have been described, all regu lated by phosphatidylserine and DAG, but only some being Co*-dependent (a, fil, fill, and j). The 8, £, £, r\, 9, i, A, and H isoforms are Ca 2+ -independent. Each isoenzyme is a single polypeptide with four conserved (C1-C4) and five variable (V1-V5) regions. Cl and C2 regions constitute the regulatory domain and contain binding sites for phospha tidylserine, Ca~, DAG, and phorbol esters, while C3 and C4 constitute the catalytic domain and contain binding sites for ATP, substrates, and various inhibitors. PKC isoenzymes are involved in a variety of cellular responses in cluding growth, differentiation, neuronal development, synoptic transmission, secretion. They were first implicated