Kato H, Kawai S, Takenawa T
Department of Pharmacology, Tokyo Metropolitan Institute of Gerontology, Japan.
Biochem Biophys Res Commun. 1988 Aug 15;154(3):959-66. doi: 10.1016/0006-291x(88)90233-1.
Oncogenic transformation has been considered to be in part a consequence of the elevated levels of 1,2-diacylglycerol(DG), resulting in the permanent activation of protein kinase C. DG content in transformed cells with v-H-ras, c-K-ras and N-ras oncogene increased 1.5-fold compared to that in non-transformed NIH/3T3 cells. DG kinase activity of membrane fractions, which plays an important role in DG attenuation, was significantly lower in all ras-transformed cells. On the contrary, DG kinase activity in cytosol fractions in ras-transformed cells was found to be increased. DG kinase translocated very markedly from cytosol to membranes in non-transformed NIH/3T3 cells by the treatment of phospholipase C. On the other hand, translocation of DG kinase in ras-transformed cells was slight, though the formation of DG by the treatment of phospholipase C was almost same between ras-transformed and NIH/3T3 cells. These results strongly support the idea that the increased DG content in ras-transformed cells is, at least partly due to the defect of DG kinase translocation, which may lead to the sustained activation of protein kinase C.
致癌转化被认为部分是1,2 -二酰甘油（DG）水平升高的结果，导致蛋白激酶C的持续激活。与未转化的NIH/3T3细胞相比，携带v-H-ras、c-K-ras和N-ras癌基因的转化细胞中的DG含量增加了1.5倍。在DG衰减中起重要作用的膜组分的DG激酶活性在所有ras转化细胞中均显著降低。相反，发现ras转化细胞中胞质溶胶组分的DG激酶活性增加。通过磷脂酶C处理，未转化的NIH/3T3细胞中的DG激酶从胞质溶胶非常明显地转移到膜上。另一方面，尽管在ras转化细胞和NIH/3T3细胞中通过磷脂酶C处理形成的DG几乎相同，但ras转化细胞中DG激酶的转移很轻微。这些结果有力地支持了这样一种观点，即ras转化细胞中DG含量的增加至少部分是由于DG激酶转移缺陷，这可能导致蛋白激酶C的持续激活。
