Bishop W R, Bell R M
Department of Biochemistry, Duke University Medical Center, Durham, North Carolina 27710.
Oncogene Res. 1988 Feb;2(3):205-18.
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.
显然，细胞内二酰甘油（DAG）水平在合成、降解和区室化水平上受到调控。这种复杂的调控使DAG能够发挥其两个不同的作用：支持甘油olipids的生物合成（和降解），以及调节蛋白激酶C（PKC）活性。关于DAG如何履行这两种功能，还需要进一步明确，尤其要着重于如何维持不同的DAG池、DAG代谢众多途径之间的相互关系，以及升高的DAG在细胞转化中所起的作用。DAG代谢的扰动可能会深刻改变细胞功能和生长控制。负责减弱DAG第二信使的酶（如DAG激酶和脂酶）的调节或活性缺陷，预计会提高质膜DAG水平。这可能导致PKC持续激活和细胞转化。在生物合成途径中利用DAG的酶（如二酰甘油酰基转移酶、胆碱和乙醇胺磷酸转移酶）的缺陷，可能会提高内质网中的DAG水平。其后果之一可能是PKC的激活，也许是在通常不会发生激活的细胞内位点。DAG经历快速的跨双层运动，并可通过一个易化过程在细胞膜之间快速转移。因此，内质网中升高的DAG池可能导致其他膜（如质膜）中DAG升高和PKC激活。因此，这些利用DAG的酶可能代表未鉴定的隐性癌基因的产物。
