Cdc2 activation in fission yeast depends on Mcs6 and Csk1, two partially redundant Cdk-activating kinases (CAKs) Journal Article
| Authors: | Lee, K. M.; Saiz, J. E.; Barton, W. A.; Fisher, R. P. |
| Article Title: | Cdc2 activation in fission yeast depends on Mcs6 and Csk1, two partially redundant Cdk-activating kinases (CAKs) |
| Abstract: | 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 Cds [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 reactive 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. |
| Keywords: | genetics; mutation; animal; cytology; metabolism; animals; cells, cultured; cell cycle; cell division; protein kinases; enzyme activation; drug effect; enzymology; protein serine threonine kinase; physiology; animalia; hybrid protein; recombinant fusion proteins; cell culture; saccharomyces cerevisiae; protein-serine-threonine kinases; temperature; adenosine triphosphate; cyclin-dependent kinases; cyclin dependent kinase; protein kinase; fungal protein; schizosaccharomyces; schizosaccharomyces pombe proteins; cyclin dependent kinase 1; cyclin dependent kinase activating kinase; cyclin-dependent kinase-activating kinase; metazoa; schizosaccharomyces pombe protein; schizosaccharomyces pombe; fungal proteins; cdc2 protein kinase; csk1 protein, s pombe; saccharomyces pombe; hemagglutinins; hemagglutinin; article |
| Journal Title: | Current Biology |
| Volume: | 9 |
| Issue: | 8 |
| ISSN: | 0960-9822 |
| Publisher: | Cell Press |
| Date Published: | 1999-04-22 |
| Start Page: | 441 |
| End Page: | 444 |
| Language: | English |
| DOI: | 10.1016/s0960-9822(99)80194-8 |
| PUBMED: | 10226032 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- Export Date: 16 August 2016 -- Source: Scopus |
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