Diacylglycerol stimulates DNA synthesis and cell division in mouse 3T3 cells: role of Ca2+-sensitive phospholipid-dependent protein kinase

Abstract

The synthetic diacylglycerol 1-oleoyl-2-acetylglycerol competes directly with [3H]phorbol 12,13-dibutyrate for common binding sites in monolayer cultures of Swiss 3T3 cells and rapidly stimulates the phosphorylation of a Mr 80,000 cellular protein that has recently been shown to reflect the activation of protein kinase C in intact cells. Thus, this diacylglycerol provided a useful tool to determine whether exogenously added diacylglycerols can mimic the potent tumor promoter phorbol ester in eliciting DNA synthesis and cell division in quiescent cells. We found that OAG acts synergistically with insulin and other growth factors to stimulate reinitiation of cell proliferation, and several lines of evidence indicate that OAG shares with phorbol esters a common pathway of mitogenic action via stimulation of protein kinase C activity in intact 3T3 cells. The findings support the hypothesis that diacylglycerols represent endogenous analogs of phorbol esters and raise the possibility that diacylglycerols generated in the plasma membrane could act as a mitogenic signal for quiescent cells.