Lipid second messenger regulation: the role of diacylglycerol kinases and their relevance to hypertension

Extracellular stimuli elicit cellular responses through generation of intra cellular second messengers. The lipid second messenger diacylglycerol is pr oduced following activation of the phosphoinositide signalling system. Diac ylglycerol is the physiological activator of protein kinase C but also inte racts indirectly with other signalling molecules such as small G proteins. Diacylglycerol kinases convert diacylglycerol to phosphatidic acid so termi nating signalling through diacylglycerol, However, phosphatidic acid itself has a lipid second messenger role, with targets distinct from those of its precursor diacylglycerol, Therefore, diacylglycerol kinases occupy a centr al position in signal transduction and regulation of their activity is cruc ial to cellular function, A family of nine mammalian diacylglycerol kinases have been identified. Their structural diversity and complex pattern of ti ssue expression suggests that they function in distinct cellular processes. In addition to the plasma membrane, diacylglycerol kinases are found at th e nucleus and cytoskeleton and translocation between subcellular compartmen ts occurs with agonist stimulation. In small arteries diacylglycerol kinase activity is increased by adrenergic stimulation implying a role in vascula r smooth muscle responses. Due to their role as key regulators of protein k inase C activity diacylglycerol kinases may play a role in the cardiovascul ar changes that occur in hypertension and as such could represent novel the rapeutic targets.