Possible involvement of RAS-encoded proteins in glucose-induced inositolphospholipid turnover in Saccharomyces cerevisiae.

Incubation of yeast Saccharomyces cerevisiae at very low (0.02%) glucose levels led to arrest of the cell cycle at the G0/G1 phase. Readdition of glucose to these "starved" yeast resulted in cell proliferation. In glucose-starved yeast, glucose stimulated 32P incorporation into phosphatidic acid, phosphatidylinositol, phosphatidylinositol monophosphate, and phosphatidylinositol bisphosphate but not into phosphatidylethanolamine and phosphatidylcholine. Preincubation of yeast with [3H]inositol and subsequent exposure to glucose resulted in rapid formation of [3H]inositol monophosphate and [3H]inositol trisphosphate, presumably derived from phosphatidylinositol and phosphatidylinositol bisphosphate. Under similar conditions, glucose elicited both efflux and influx of Ca2+ in yeast. Glucose-induced 32P incorporation into inositolphospholipids and formation of [3H]inositol phosphates were more pronounced in RAS-related mutants such as ras1, ras1 ras2 bcy1, and RAS2Val19 than in the wild-type strain. These results strongly suggest that glucose stimulates inositolphospholipid turnover, Ca2+ mobilization, and subsequent cell proliferation in a manner similar to that of growth factors with mammalian cells, and that RAS-encoded proteins are involved in regulation of this glucose-induced inositolphospholipid turnover in yeast.