Cdc2 activation in fission yeast depends on Mcs6 and Csk1, two partially redundant Cdk-activating kinases (CAKs).
Cyclin-dependent kinases (Cdks) are fully active only when phosphorylated by a Cdk-activating kinase (CAK) [1]. Metazoan CAK is itself a Cdk, Cdk7, whereas the CAK of Saccharomyces cerevisiae is a distinct enzyme unrelated to Cdks [1]. The Mcs6-Mcs2 complex of Schizosaccharomyces pombe is a putative CAK related to the metazoan ... enzyme [2] [3]. Although the loss of Mcs6 is lethal, it results in a phenotype that is inconsistent with a failure to activate Cdc2, the major Cdk in S. pombe [3]. We therefore tested the ability of Csk1, a putative regulator of Mcs6 [4], to activate Cdk-cyclin complexes in vitro. Csk1 activated both the monomeric and the Mcs2-bound forms of Mcs6. Surprisingly, Csk1 also activated Cdc2 in complexes with either Cdc13 or Cig2 cyclins. When a double mutant carrying a csk1 deletion and a temperature-sensitive mcs6 allele was incubated at the restrictive temperature, Cdc2 was not activated and the cells underwent a cell division arrest prior to mitosis. Cdc2-cyclin complexes isolated from the arrested cells could be activated in vitro by recombinant CAK, whereas complexes from wild-type cells or either of the single mutants were refractory to activation. Thus, fission yeast contains two partially redundant CAKs: the Mcs6-Mcs2 complex and Csk1. Inactivation of both CAKs is necessary and sufficient to prevent Cdc2 activation and cause a cell-cycle arrest. Mcs6, which is essential, may therefore have required functions other than Cdk activation.
Mesh Terms:
Adenosine Triphosphate, Animals, CDC2 Protein Kinase, Cell Cycle, Cell Division, Cells, Cultured, Cyclin-Dependent Kinases, Enzyme Activation, Fungal Proteins, Hemagglutinins, Mutation, Protein Kinases, Protein-Serine-Threonine Kinases, Recombinant Fusion Proteins, Schizosaccharomyces, Schizosaccharomyces pombe Proteins, Temperature
Adenosine Triphosphate, Animals, CDC2 Protein Kinase, Cell Cycle, Cell Division, Cells, Cultured, Cyclin-Dependent Kinases, Enzyme Activation, Fungal Proteins, Hemagglutinins, Mutation, Protein Kinases, Protein-Serine-Threonine Kinases, Recombinant Fusion Proteins, Schizosaccharomyces, Schizosaccharomyces pombe Proteins, Temperature
Curr. Biol.
Date: Apr. 22, 1999
PubMed ID: 10226032
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