THE CDC25 PROTEIN OF SACCHAROMYCES-CEREVISIAE IS REQUIRED FOR NORMAL GLUCOSE-TRANSPORT

The essential CDC25 gene product of Saccharomyces cerevisiae is the mo st upstream known component of the RAS/adenylate cyclase pathway. Cdc2 5 is a GTP-exchange protein involved in activating RAS in response to fermentable carbon sources. In this paper it is reported that the Cdc2 5 protein, in addition to its stimulatory role in the RAS/adenylate cy clase pathway, regulates glucose transport. Continuous culture studies and glucose uptake experiments showed that the cdc25-1 and the cdc25- 5 temperature-sensitive mutants exhibit decreased glucose uptake activ ity at the restrictive temperature under both repressed and derepresse d conditions as compared to the wild-type strain. Because the cdc25-1 mutant is not impaired in its cAMP metabolism, it is concluded that th is effect on glucose transport is independent of cAMP levels. Furtherm ore, it is shown that the decrease in glucose uptake activity is not d ue to a decrease in protein synthesis or to an arrest in the G1 phase of the cell cycle. In addition to a defect in glucose uptake, the cdc2 5-5 mutant strain exhibited differences in glucose metabolism, probabl y due to the decreased cAMP level and hence decreased protein kinase A activity. Because the Cdc25 protein is localized at the membrane, the se results indicate that Cdc25 is directly involved in glucose transpo rt and may be in direct contact with the glucose transporters.