Stimulation of cell proliferation and polyphosphoinositide turnover in a yeast sterol auxotroph by ergosterol

The effect of ergosterol on cell division and phospholipid metabolism was investigated in strain GL7, a sterol auxotroph of Saccharmyces cerevisiae. When starved for ergosterol GL7 remains viable but grows very slowly and partially accumulates in the unbudded state. The readdition of ergosterol alone or together with cholesterol but not cholesterol alone stimulates both budding and cell proliferation noticeably after a lag of several hours. Within 10 min after ergosterol readdition to prelabeled cholesterol-grown cells the /sup 32/P and (/sup 3/H) inositol content of the polyphosphoinositides increases markedly followed by an equally striking and rapid decrease. The phosphatidylinositol kinase activity in the membrane fraction also increases when cells growing on cholesterol were supplemented with a small amount of ergosterol. A serine specific casein kinase activity which is immunoprecipitable by antibody prepared against the Rous sarcoma virus transforming protein, pp60/sup v-src/, is enhanced in ergosterol-grown cells when compared to the kinase activity in cholesterol cells. Taken together the results suggest that increased poly-phosphoinositide turnover and protein phosphorylation are associated with or parallel the stimulation of cell proliferation by a small amount of the yeast's natural sterol.