Disappearance of diacylglycerol kinase translocation in ras-transformed cells.
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.
Kato
H
H
Department of Pharmacology, Tokyo Metropolitan Institute of Gerontology, Japan.
Kawai
S
S
Takenawa
T
T
D000818:Animals; D002462:Cell Membrane / Q000201:enzymology; D002471:Cell Transformation, Neoplastic; D002478:Cells, Cultured; D003600:Cytosol / Q000201:enzymology; D019852:Diacylglycerol Kinase; D011905:Genes, ras; D007700:Kinetics; D051379:Mice; D010770:Phosphotransferases / Q000378:metabolism*
D010770:Phosphotransferases; D019852:Diacylglycerol Kinase