Roles of Wee1 and Nim1 protein kinases in regulating the switch from mitotic division to sexual development in Schizosaccharomyces pombe.
In self-fertile strains of the fission yeast Schizosaccharomyces pombe, nitrogen starvation initiates a program of sexual development in which cells express mating pheromones and receptors, arrest cell cycle progression in G1, and conjugate. This process is dependent on Rum1, an inhibitor of the Cdc2-Cdc13 and Cdc2-Cig2 cyclin B kinases. The M-phase induction activity of Cdc2-Cdc13 is inhibited by Wee1 tyrosine kinase, which phosphorylates Cdc2 on tyrosine-15. We report here that Wee1 activity is also important for mating. This discovery arose from studies of Nim1, a kinase which promotes mitosis by inhibiting Wee1. Nim1 was previously thought to have an important role in promoting mitosis during nitrogen starvation, but our studies revealed that Nim1 protein drops to an undetectable level within 15 min of nitrogen depletion. In contrast, Wee1 remains abundant, and tyrosine-phosphorylated Cdc2 is detected for at least 4 h after resuspension of cells in nitrogen-free medium. This suggested that maintenance of Wee1 activity may be important during the early stages of nitrogen starvation, a proposal confirmed by the observation that mating efficiency is reduced ca. fivefold in wee1- cells. Transcriptional induction of genes encoding mating factors and receptors is also delayed in wee1- cells. The wee1- mating defect is suppressed by deletion of cig2+, which encodes a B-type cyclin that promotes the onset of S and inhibits conjugation. These findings indicate that Wee1 and Rum1 act jointly to inhibit Cdc2 and promote sexual development in nitrogen-starved cells.
Wu
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Department of Molecular Biology, Scripps Research Institute, La Jolla, California 92037, USA.
Russell
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P
D000643:Ammonium Chloride / Q000494:pharmacology; D016203:CDC2 Protein Kinase / Q000378:metabolism; D018797:Cell Cycle Proteins; D003227:Conjugation, Genetic; D019926:Cyclin B; D016213:Cyclins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D005656:Fungal Proteins; D015966:Gene Expression Regulation, Fungal / Q000235:genetics; D008938:Mitosis / Q000502:physiology*; D009154:Mutation; D009584:Nitrogen / Q000502:physiology; D009687:Nuclear Proteins; D010675:Pheromones; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D021382:Protein Sorting Signals / Q000235:genetics; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D012331:RNA, Fungal / Q000032:analysis; D012333:RNA, Messenger / Q000032:analysis; D051964:Receptors, Mating Factor; D018000:Receptors, Peptide / Q000235:genetics; D012098:Reproduction; D012568:Schizosaccharomyces / Q000201:enzymology / Q000235:genetics / Q000254:growth & development*; D029702:Schizosaccharomyces pombe Proteins; D014157:Transcription Factors / Q000235:genetics; D014443:Tyrosine / Q000378:metabolism
D018797:Cell Cycle Proteins; C080328:Cig2 protein, S pombe; D019926:Cyclin B; D016213:Cyclins; D005656:Fungal Proteins; D009687:Nuclear Proteins; D010675:Pheromones; D021382:Protein Sorting Signals; D012331:RNA, Fungal; D012333:RNA, Messenger; D051964:Receptors, Mating Factor; D018000:Receptors, Peptide; D029702:Schizosaccharomyces pombe Proteins; D014157:Transcription Factors; C085847:map2 protein, S pombe; D000643:Ammonium Chloride; D014443:Tyrosine; C080364:cdr1 protein, S pombe; C068689:wee1 protein, S pombe; D011505:Protein-Tyrosine Kinases; D017346:Protein Serine-Threonine Kinases; D016203:CDC2 Protein Kinase; D009584:Nitrogen