Essential role for phosphatidylinositol 4,5-bisphosphate in yeast cell proliferation

The responses of mammalian cells to external signals are commonly mediated by intracellular secondary messengers, among which are the breakdown products of phosphatidylinositol 4,5-bisphosphate (PIP2): 1,2-diacylglycerol (DG) and inositol 1,4,5-triphosphate (IP3) (refs 1-7). Although phosphoinositide turnover in the yeast Saccharomyces cerevisiae has been shown to be regulated by glucose and sterol, as yet no definitive function has been ascribed to yeast phosphoinositides. We have recently developed a monoclonal antibody specific for PIP2 and reported that it inhibits mitogenesis of mammalian cells stimulated by platelet-derived growth factor and bombesin. We now report that when introduced into yeast cells by electroporation this antibody inhibits their growth. Furthermore, several yeast mutants with temperature-dependent growth defects are altered in their sensitivity to our antibody and are found to have specific alterations in their phosphoinositide metabolism.