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Dephosphorylation of cyclin-dependent kinases by type 2C protein phosphatases
Open accessAbstract
Activating phosphorylation of cyclin-dependent protein kinases (CDKs) is necessary for their kinase activity and cell cycle progression. This phosphorylation is carried out by the Cdk-activating kinase (CAK); in contrast, little is known about the corresponding protein phosphatase. We show that type 2C protein phosphatases (PP2Cs) are responsible for this dephosphorylation of Cdc28p, the major budding yeast CDK. Two yeast PP2Cs, Ptc2p and Ptc3p, display Cdc28p phosphatase activity in vitro and in vivo, and account for approximately 90% of Cdc28p phosphatase activity in yeast extracts. Overexpression of PTC2 or PTC3 results in synthetic lethality in strains temperature-sensitive for yeast CAK1, and disruptions of PTC2 and PTC3 suppress the growth defect of a cak1 mutant. Furthermore, PP2C-like enzymes are the predominant phosphatases toward human Cdk2 in HeLa cell extracts, indicating that the substrate specificity of PP2Cs toward CDKs is evolutionarily conserved.
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Cites
How Proteolysis Drives the Cell Cycle
King, R. W., Deshaies, R. J., Peters, J.-M., & Kirschner, M. W. (1996) · Science · doi:10.1126/science.274.5293.1652 · Cited by 1,273
Cited by
PPM1A Functions as a Smad Phosphatase to Terminate TGFβ Signaling
Lin, X., Duan, X., Liang, Y.-Y., Su, Y., Wrighton, K. H., Long, J., Hu, M., Davis, C. M., Wang, J., Brunicardi, F. C., et al. (2006) · Cell · doi:10.1016/j.cell.2006.03.044 · Cited by 485
Biological Physics of the Developing Embryo
Forgacs, G., & Newman, S. A. (2005) · doi:10.1017/cbo9780511755576 · Cited by 339
Metadata
- Authors
- Cheng, A., Ross, K. E., Kaldis, P., & Solomon, M. J.
- Venue
- Genes & Development
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 1999-11-15
- Volume
- 13
- Issue
- 22
- Pages
- 2946-2957
- ISSN
- 0890-9369 (ISSN-L)
- OpenAlex
- W2069526853
- Cited by
- 168
- References
- 1
- Type
- posted content
- Language
- en
- Open access
- diamond
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- Cheng, A., Ross, K. E., Kaldis, P., & Solomon, M. J. (1999). Dephosphorylation of cyclin-dependent kinases by type 2C protein phosphatases. Genes & Development. https://doi.org/10.1101/gad.13.22.2946
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