Novel source of 1,2-diacylglycerol elevated in cells transformed by Ha-ras oncogene

Abstract

Genes involved in the transduction of signals required for normal cell proliferation commonly appear to be subverted in the neoplastic process¹. One such group is the highly conserved family of ras genes, which have been detected as transforming genes in a wide variety of naturally occurring tumours. By analogy with other known G proteins², the p21 proteins encoded by ras genes may act as regulatory proteins in the transduction of signals that lead to DNA synthesis. A major pathway involved in the DNA synthesis induced by growth factors is mediated by phosphatidylinositol turnover: cleavage of phosphoinositides by phospholipase C produces 1,2-diacylglycerol, and inositol phosphates³. The former acts as an essential cofactor for protein kinase C (ref. 4), and inositol-(l,4,5)-triphosphate mobilizes Ca²⁺ from non-mitochondrial intracellular stores⁵. We demonstrate a reproducible increase in 1,2-diacylglycerol, in the absence of a detectable increase in inositol phosphates, in transformed cells containing Ha-ras oncogenes and with different membrane targeting signals for the ras p21 protein. These findings suggest that a source other than phosphoinositides exists for the generation of 1,2-diacylglycerol and that the Ha-ras oncogene specifically activates this novel pathway for 1,2-diacylglycerol production.