82 - Protein Kinase C

Summary

The discovery of protein kinase C (PKC) by Y. Nishizuka and colleagues in the late 1970s was a landmark event in biology and reinforced the emerging concept at the time that extracellular agonists that stimulate receptor-mediated phospholipid hydrolysis transduce signals through the activation of a variety of serine/threonine protein kinases (1). In this context, the discovery of PKC was particularly illuminating because it also became evident that this kinase serves as the receptor for potent tumor-promoting phorbol esters, which mimic the natural allosteric activator of PKC, diacylglycerol (DAG) (2). These findings propelled the nascent PKC field into one of the most widely studied lipid second-messenger signaling pathways, which has occupied researchers in the last two decades (3). Studies to date have painted a detailed molecular picture of the mechanisms that control PKC activation, localization, and function. Thus, at the dawn of the new millennium, the spatial and temporal controls of PKC regulation by lipid activators and by phosphorylation are now well understood. Although this knowledge has allowed researchers to foray into more complex questions about how PKC transduces signals to modulate cellular responses, this area of investigation lags significantly behind.

This chapter reviews the mechanisms by which PKC functions as a signal-relay enzyme in the endothelium. Although our understanding of the role of PKC in vascular biology and pathology is still in its infancy, studies have clearly identified this kinase as a key regulator of signal coupling in endothelial cells (ECs) and have thus provided exciting prospects for translating this information into therapeutic value.