Nim1 kinase promotes mitosis by inactivating Wee1 tyrosine kinase.
In most species, including the fission yeast Schizosaccharomyces pombe, the Cdc2/cyclin B mitosis-inducing kinase is maintained in an inhibited state during interphase as a result of phosphorylation of a tyrosine residue in the ATP-binding region of Cdc2 (refs 1-3). This site is phosphorylated by Wee1 kinase and dephosphorylated by Cdc25 phosphatase. In fission yeast an additional element of the G2/M control Nim1/Cdr1 kinase, has been identified which functions as a potent mitotic inducer. These studies suggested that Nim1 acts by inhibiting Wee1, perhaps by direct phosphorylation. Consistent with this model, we report here that Wee1 is hyperphosphorylated in cells that overproduce Nim1. Likewise, Wee1 phosphorylation is reduced in nim1- cells. Highly purified Nim1 kinase phosphorylates Wee1 in vitro, resulting in strong inhibition of Wee1 kinase. These observations show that Nim1 promotes the onset of mitosis by inhibiting Wee1.
Department of Molecular Biology, Scripps Research Institute, La Jolla 92037.
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D000804:Angiotensin II / Q000378:metabolism; D000818:Animals; D018797:Cell Cycle Proteins; D002460:Cell Line; D003001:Cloning, Molecular; D005656:Fungal Proteins / Q000378:metabolism; D005982:Glutathione Transferase / Q000235:genetics; D006133:Growth Substances / Q000235:genetics / Q000378:metabolism*; D008938:Mitosis; D009036:Moths; D009687:Nuclear Proteins; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012568:Schizosaccharomyces / Q000166:cytology* / Q000201:enzymology / Q000378:metabolism; D029702:Schizosaccharomyces pombe Proteins; D020666:ras-GRF1
D018797:Cell Cycle Proteins; D005656:Fungal Proteins; D006133:Growth Substances; D009687:Nuclear Proteins; D047428:Protein Kinase Inhibitors; D011993:Recombinant Fusion Proteins; D029702:Schizosaccharomyces pombe Proteins; D020666:ras-GRF1; D000804:Angiotensin II; D005982:Glutathione Transferase; C080364:cdr1 protein, S pombe; C068689:wee1 protein, S pombe; D011505:Protein-Tyrosine Kinases; D017346:Protein Serine-Threonine Kinases