Takuwa N, Takuwa Y, Rasmussen H
Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut 06510.
J Biol Chem. 1988 Jul 15;263(20):9738-45.
1-Monooleoylglycerol (MOG), a recently reported diacylglycerol kinase inhibitor (Bishop, W. R., Ganong, B. R., and Bell, R. M. (1986) J. Biol. Chem. 261, 6993-7000), exerts potent stimulatory effects on [3H]thymidine incorporation into DNA and glucose transport in Swiss 3T3 fibroblasts. MOG induces a rapid and sustained 2.5-fold increase in the cellular 1,2-diacylglycerol (1,2-DG) content, and phosphorylation of an acidic 80-kDa protein, a putative substrate for the protein kinase C (Ca2+/phospholipid-dependent protein kinase). The effect of MOG is additive to that of bombesin in terms of both an increase in tissue diacylglycerol content and phosphorylation of the 80-kDa proteins. In addition to these effects, MOG potently stimulates release of arachidonic acid from phospholipids. Inhibitors of cyclooxygenase and lipoxygenase have little effect, if any, on MOG-induced stimulation of glucose transport and DNA synthesis, while exogenously applied arachidonic readily stimulates both of these cellular responses. Furthermore, arachidonic acid, at its biologically active concentrations, is found to induce a rapid and sustained increase in cellular 1,2-DG content and stimulate the phosphorylation of the 80-kDa protein, although to a lesser extent than MOG. Prolonged pretreatment of the cells with phorbol 12,13-dibutyrate, which reduces the cellular protein kinase C content, markedly attenuates the effects of both MOG and arachidonic acid on glucose transport and DNA synthesis. These data indicate that MOG increases endogenous 1,2-DG content and thereby acts as a potent activator of protein kinase C, and that activation of protein kinase C is a crucial step in MOG-induced stimulation of mitogenesis and glucose transport.
1-单油酰甘油（MOG）是最近报道的一种二酰基甘油激酶抑制剂（毕晓普，W.R.，加农，B.R.，以及贝尔，R.M.（1986年）《生物化学杂志》261卷，6993 - 7000页），对瑞士3T3成纤维细胞中[3H]胸苷掺入DNA以及葡萄糖转运具有强大的刺激作用。MOG能使细胞内1,2 - 二酰基甘油（1,2 - DG）含量迅速且持续增加2.5倍，并使一种酸性80 kDa蛋白发生磷酸化，该蛋白被认为是蛋白激酶C（Ca2 + /磷脂依赖性蛋白激酶）的底物。就组织二酰基甘油含量增加和80 kDa蛋白磷酸化而言，MOG的作用与蛙皮素的作用具有相加性。除了这些作用外，MOG还能有力地刺激花生四烯酸从磷脂中释放出来。环氧化酶和脂氧合酶抑制剂对MOG诱导的葡萄糖转运和DNA合成刺激作用几乎没有影响（如果有影响的话），而外源性施加的花生四烯酸很容易刺激这两种细胞反应。此外，在其生物活性浓度下，花生四烯酸能使细胞内1,2 - DG含量迅速且持续增加，并刺激80 kDa蛋白的磷酸化，尽管程度比MOG小。用佛波醇12,13 - 二丁酸酯对细胞进行长时间预处理，可降低细胞内蛋白激酶C含量，显著减弱MOG和花生四烯酸对葡萄糖转运和DNA合成的作用。这些数据表明，MOG增加内源性1,2 - DG含量，从而作为蛋白激酶C的有效激活剂发挥作用，并且蛋白激酶C的激活是MOG诱导的有丝分裂和葡萄糖转运刺激过程中的关键步骤。
