Most hormones, neurotransmitters, and other signalling molecules stimulate receptors that are coupled to the generation of the second messengers cAMP, diacylglycerol, and Ca2+. These second messenger systems enable coordin ated cellular responses to a single stimulus. Studies on cAMP and di acylglyerol have established that their effects are mediated by general or multifunctional protein kinases that phosphorylate numerous substrates and thereby integrate related functions. Protein kinase C (PKC) mediates the actions of diacylglycerol, while cAMP-dependent protein kinase (PKA) is the primary mediator of cAMP.

Ca2+ plays a central role as a second messenger with a regulatory involve ment in many aspects of cellular signalling. Intracellular Ca2+ levels are buffered to a low concentration (ca. 100 nM), and rapidly rise to levels of I JLM or more in response to incoming signals. In contrast to the few mediators of cAMP and diacylglycerol, a variety of proteins and enzymes mediate intracellular responses to Ca2+. In many cells, calmodulin is the predominant intracellular" Ca2+-receptor" that activates enzymes in response to Ca2+. Protein kinases are prominent among these, and a number of Ca2+/calmodulin-activated protein kinases have been described in both neuronal and non-neuronal tissues. Several, including myosin light chain kinase (MLCK), phosphorylase kinase, and CaM kinase III (an elongation factor-2 kinase), are dedicated to the phosphorylation and regulation of only a single class of substrate. These enzymes have been primarily studied in non neuronal tissues; the reader is referred to recent reviews of these fields (1-4). Despite this diversity of Ca2+ mediators, a general or multifunctional kinase mediating the effects of Ca2+ has also been identified, and this enzyme is the major focus of this review.