Disappearance of diacylglycerol kinase translocation in ras-transformed cells

Abstract

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 markedky 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.