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Inactivation of the p34 cdc2 -Cyclin B Complex by the Human WEE1 Tyrosine Kinase
Abstract
Entry into mitosis in Schizosaccharomyces pombe is negatively regulated by the wee1 + gene, which encodes a protein kinase with serine-, theonine-, and tyrosine-phosphorylating activities. The wee1 + kinase negatively regulates mitosis by phosphorylating p34 cdc2 on tyrosine 15, thereby inactivating the p34 cdc2 -cyclin B complex. The human homolog of the wee1 + gene ( WEE1Hu ) was overproduced in bacteria and assayed in an in vitro system. Unlike its fission yeast homolog, the product of the WEE1Hu gene encoded a tyrosine-specific protein kinase. The human WEE1 kinase phosphorylated the p34 cdc2 -cyclin B complex on tyrosine 15 but not on threonine 14 in vitro and inactivated the p34 cdc2 -cyclin B kinase. This inhibition was reversed by the human Cdc25C protein, which catalyzed the dephosphorylation of p34 cdc2 . These results indicate that the product of the WEE1Hu gene directly regulates the p34 cdc2 -cyclin B complex in human cells and that a kinase other than that encoded by WEE1Hu phosphorylates p34 cdc2 on threonine 14.
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Citations
Cited by
Morgan, D. O. (1995) · Nature · doi:10.1038/374131a0 · Cited by 3,284
Cdi1, a human G1 and S phase protein phosphatase that associates with Cdk2
Gyuris, J. (1993) · Cell · doi:10.1016/0092-8674(93)90498-f · Cited by 1,522
The Global Phosphorylation Landscape of SARS-CoV-2 Infection
Bouhaddou, M., Memon, D., Meyer, B., White, K. M., Rezelj, V. V., Correa Marrero, M., Polacco, B. J., Melnyk, J. E., Ulferts, S., Kaake, R. M., et al. (2020) · Cell · doi:10.1016/j.cell.2020.06.034 · Cited by 1,020
Bretones, G., Delgado, M. D., & León, J. (2015) · Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms · doi:10.1016/j.bbagrm.2014.03.013 · Cited by 747
Hirai, H., Iwasawa, Y., Okada, M., Arai, T., Nishibata, T., Kobayashi, M., Kimura, T., Kaneko, N., Ohtani, J., Yamanaka, K., et al. (2009) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-09-0463 · Cited by 540
Metadata
- Authors
- Parker, L. L., & Piwnica-Worms, H.
- Venue
- Science
- Published
- 1992-09-25
- Volume
- 257
- Issue
- 5078
- Pages
- 1955-1957
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2038143768
- Cited by
- 716
- References
- 0
- FWCI
- 12.18
- Type
- journal article
- Language
- en
- Open access
- closed
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- Parker, L. L., & Piwnica-Worms, H. (1992). Inactivation of the p34 cdc2 -Cyclin B Complex by the Human WEE1 Tyrosine Kinase. Science. https://doi.org/10.1126/science.1384126
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