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 sensing and growth control. Under nutrient-limiting conditions, slk1 mutants fail to undergo cell cycle arrest. The role of the SLK1 protein in nutrient sensing was examined with respect to the cAMP-dependent protein kinase (PKA) pathway, which has a well characterized role in growth control in yeast, and by the analysis of dominant SLK1 alleles that affect the nutrient response of wild-type cells. Interactions with the PKA pathway were examined by phenotypic analysis of double mutants of slk1 and various PKA pathway mutants. Combining the slk1-delta mutation with a mutation that is thought constitutively activate the PKA pathway, pde2, resulted in enhanced growth control defects. The combination of slk1-delta with mutations that inhibit the PKA pathway, cdc25 and ras1, ras2, failed to alleviate the slk1 cell cycle arrest defect and lowered the permissive temperature for growth. Furthermore bcy1 tpk1 tpk2 tpk3w (bcy1 tpkw) mutants, which have constitutive, low-level, cAMP-independent kinase activity, exhibit nutrient sensing, which is eliminated in the slk1 bcy1 tpkw 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 regulation of SLK1 function in growth control. Overexpression of this region caused starvation sensitivity in wild-type cells by interfering with SLK1 protein function.
Costigan
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C
Department of Biology, Yale University, New Haven, CT 06511.
Snyder
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D000595:Amino Acid Sequence; D001483:Base Sequence; D002455:Cell Division; D017868:Cyclic AMP-Dependent Protein Kinases / Q000502:physiology; D005656:Fungal Proteins / Q000235:genetics / Q000502:physiology*; D011905:Genes, ras; D020929:Mitogen-Activated Protein Kinase Kinases; D008969:Molecular Sequence Data; D009154:Mutation; D011494:Protein Kinases / Q000235:genetics / Q000502:physiology*; D012045:Regulatory Sequences, Nucleic Acid; D012441:Saccharomyces cerevisiae / Q000201:enzymology*; D029701:Saccharomyces cerevisiae Proteins; D013012:Sorbitol / Q000494:pharmacology
D005656:Fungal Proteins; D029701:Saccharomyces cerevisiae Proteins; D013012:Sorbitol; D011494:Protein Kinases; C072075:BCK1 protein, S cerevisiae; D017868:Cyclic AMP-Dependent Protein Kinases; D020929:Mitogen-Activated Protein Kinase Kinases