Functions of diacylglycerol in glycerolipid metabolism, signal transduction and cellular transformation.

Clearly, cellular DAG levels are regulated at the levels of synthesis, degradation and compartmentalization. This complex regulation enables DAG to perform its two distinct roles: supporting the biosynthesis (and degradation) of glycerolipids, and regulating PKC activity. Further definition is needed as to how DAG fulfills both functions, with particular emphasis on how distinct DAG pools are maintained, the interrelationships between the numerous pathways of DAG metabolism, and the role which elevated DAG plays in cellular transformation. Cellular function and growth control may be profoundly altered by perturbation of DAG metabolism. Defects in the regulation or the activity of enzymes responsible for attenuation of DAG second messengers (eg. DAG kinase and lipase) would be expected to elevate plasma membrane DAG levels. This could lead to persistent PKC activation and cellular transformation. Defects in the enzymes which utilize DAG in the biosynthetic pathway (eg. diacylglycerol acyltransferase, and choline and ethanolamine phosphotransferases) could elevate DAG levels in the ER. One consequence of this could be activation of PKC, perhaps at intracellular sites where activation does not normally occur. DAG undergoes rapid transbilayer movement and can be rapidly transferred between cellular membranes by a facilitated process. Therefore, elevated pools of DAG in the ER may lead to elevated DAG in other membranes (eg. plasma membrane) and PKC activation. These DAG utilizing enzymes may, therefore, represent products of unidentified recessive oncogenes.