Potential regulation of Ste20 function by the Cln1-Cdc28 and Cln2-Cdc28 cyclin-dependent protein kinases.
The activity of the Saccharomyces cerevisiae pheromone signal transduction pathway is regulated by Cln1/2-Cdc28 cyclin-dependent kinase. High level expression of CLN2 can repress activation of the pathway by mating factor or by deletion of the alpha-subunit of the heterotrimeric G-protein. We now show that CLN2 overexpression can also repress FUS1 induction if the signaling pathway is activated at the level of the beta-subunit of the G-protein (STE4) but not when activated at the level of downstream kinases (STE20 and STE11) or at the level of the transcription factor STE12. This epistatic analysis indicates that repression of pheromone signaling pathway by Cln2-Cdc28 kinase takes place at a level around STE20. In agreement with this, a marked reduction in the electrophoretic mobility of the Ste20 protein is observed at the time in the cell cycle of maximal expression of CLN2. This mobility change is constitutive in cells overexpressing CLN2 and absent in cells lacking CLN1 and CLN2. These changes in electrophoretic mobility correlate with repression of pheromone signaling and suggest Ste20 as a target for repression of signaling by G1 cyclins. Two morphogenic pathways for which Ste20 is essential, pseudohyphal differentiation and haploid-invasive growth, also require CLN1 and CLN2. Together with the previous observation that Cln1 and Cln2 are required for the function of Ste20 in cytokinesis, this suggests that Cln1 and Cln2 regulate the biological activity of Ste20 by promoting morphogenic functions, while inhibiting the mating factor signal transduction function.
Oehlen
L J
LJ
Rockefeller University, New York, New York 10021, USA. bert.oehlen@cadus.com
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D017489:CDC28 Protein Kinase, S cerevisiae / Q000378:metabolism*; D016213:Cyclins / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D004843:Epistasis, Genetic; D047908:Intracellular Signaling Peptides and Proteins; D020930:MAP Kinase Kinase Kinases; D000072235:Mating Factor; D010455:Peptides / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins; D015398:Signal Transduction
C082719:CLN1 protein, S cerevisiae; C082721:CLN2 protein, S cerevisiae; D016213:Cyclins; D047908:Intracellular Signaling Peptides and Proteins; D010455:Peptides; D029701:Saccharomyces cerevisiae Proteins; D000072235:Mating Factor; D017346:Protein Serine-Threonine Kinases; D017489:CDC28 Protein Kinase, S cerevisiae; D020930:MAP Kinase Kinase Kinases; C078754:STE20 protein, S cerevisiae