SLK1, A YEAST HOMOLOG OF MAP KINASE ACTIVATORS, HAS A RAS CAMP INDEPENDENT ROLE IN NUTRIENT SENSING/

The Saccharomyces cerevisiae SLK1 protein is implicated in nutrient se nsing and growth control. Under nutrient-limiting conditions, slk1 mut ants fail to undergo cell cycle arrest. The role of the SLK1 protein i n nutrient sensing was examined with respect to the cAMP-dependent pro tein kinase (PKA) pathway, which has a well characterized role in grow th control in yeast, and by the analysis of dominant SLK1 alleles that affect the nutrient response of wild-type cells. Interactions with th e PKA pathway were examined by phenotypic analysis of double mutants o f slk1 and various PKA pathway mutants. Combining the slk1-Delta mutat ion with a mutation that is thought constitutively activate the PKA pa thway, pde2, resulted in enhanced growth control defects. The combinat ion of slk1-Delta with mutations that inhibit the PKA pathway, cdc25 a nd ras1 ras2, failed to alleviate the slk1 cell cycle arrest defect an d lowered the permissive temperature for growth. Furthermore bcy1 tpk1 tpk2 tpk3(w) (bcy1 tpk(w)) mutants, which have constitutive, low-leve l, cAMP-independent kinase activity, exhibit nutrient sensing, which i s eliminated in the slk1 bcy1 tpk(w) mutants. These results implicated SLK1 in PKA-independent growth control in yeast. The amino-terminal, noncatalytic region of the SLK1 protein may be important in the regula tion of SLK1 function in growth control. Overexpression of this region caused starvation sensitivity in wild-type cells by interfering with SLK1 protein function.