There is now much evidence to suggest that protein kinase-C (PKC) acts as a transducer element in cell-signalling processes following stimulation of membrane receptors linked to phospholipase(s)-C (PLC). Occupancy of such receptors by specific agonists (hormones, neurotransmitters, growth factors etc.) promotes hydrolysis by PLC of the membrane phospholipid, phosphatidylinositol 4,5 bisphosphate to yield the second-messengers inositol 1,4,5, trisphosphate (IP3) and 1,2, sn diacylglycerol (DAG). Because IP3 and DAG are rapidly metabolized, their intracellular levels are raised only transiently following receptor stimulation. However, in cells expressing certain oncogenes (e.g. NRK cells transformed with K-ras or sis) the resting levels are elevated, possibly because the oncogene products function as receptor-transducer elements (for review see Berridge, 1986). Being lipid soluble, DAG remains in the plasma membrane where it is available to activate PKC which translocates from the cytoplasm to the cell membrane following cell stimulation. The conformational change to specific intracellular proteins brought about through phosphorylation by PKC is an early event in a cascade of similar biochemical reactions that either propagate or abrogate the initial signal, leading to a variety of cellular responses. There are many examples where the activation of PKC augments cellular responses brought about by an increase in intracellular free Ca2+. However, there are also examples where activation of PKC, without a concomitant increase of Ca2+ above resting levels, also provokes a response (e.g. Di Virgilio et al., 1984). Thus, the contribution of PKC activity to cellular functions varies not only among different cell types but also between different functions within the same cell.
KeywordsPhorbol Ester Mixed Micelle Porcine Aortic Endothelial Cell United Kingdom Introduction PDBu Binding
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