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Cell cycle regulation of a Xenopus Wee1-like kinase

Mueller, Paul R. and Coleman, Thomas R. and Dunphy, William G. (1995) Cell cycle regulation of a Xenopus Wee1-like kinase. Molecular Biology of the Cell, 6 (1). pp. 119-134. ISSN 1059-1524. PMCID PMC275819. https://resolver.caltech.edu/CaltechAUTHORS:MUEmbc95

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Abstract

Using a polymerase chain reaction-based strategy, we have isolated a gene encoding a Wee1-like kinase from Xenopus eggs. The recombinant Xenopus Wee1 protein efficiently phosphorylates Cdc2 exclusively on Tyr- 15 in a cyclin-dependent manner. The addition of exogenous Wee1 protein to Xenopus cell cycle extracts results in a dose-dependent delay of mitotic initiation that is accompanied by enhanced tyrosine phosphorylation of Cdc2. The activity of the Wee1 protein is highly regulated during the cell cycle: the interphase, underphosphorylated form of Wee1 (68 kDa) phosphorylates Cdc2 very efficiently, whereas the mitotic, hyperphosphorylated version (75 kDa) is weakly active as a Cdc2-specific tyrosine kinase. The down-modulation of Wee1 at mitosis is directly attributable to phosphorylation, since dephosphorylation with protein phosphatase 2A restores its kinase activity. During interphase, the activity of this Wee1 homolog does not vary in response to the presence of unreplicated DNA. The mitosis-specific phosphorylation of Wee1 is due to at least two distinct kinases: the Cdc2 protein and another activity (kinase X) that may correspond to an MPM-2 epitope kinase. These studies indicate that the down-regulation of Wee1-like kinase activity at mitosis is a multistep process that occurs after other biochemical reactions have signaled the successful completion of S phase.


Item Type:Article
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC275819/PubMed CentralArticle
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ORCID:
AuthorORCID
Dunphy, William G.0000-0001-7598-8939
Additional Information:Copyright © 1995 by The American Society for Cell Biology. Under the License and Publishing Agreement, authors grant to the general public, effective two months after publication of (i.e.,. the appearance of) the edited manuscript in an online issue of MBoC, the nonexclusive right to copy, distribute, or display the manuscript subject to the terms of the Creative Commons–Noncommercial–Share Alike 3.0 Unported license (http://creativecommons.org/licenses/by-nc-sa/3.0). Submitted October 21, 1994; Accepted December 5, 1994. Monitoring Editor: Tim Hunt We thank A. Kumagai for generously providing the baculovirus constructs for histidine-tagged human cyclin B1 and the various Cdc2 mutants. We are grateful to D. Morgan (University of California, San Francisco) for supplying the baculovirus transfer vector for histidine tagging. J. Kuang (M.D. Anderson Cancer Center) kindly provided MPM-2 antibodies. This work was supported by grants from the National Institutes of Health, Lucille P. Markey Charitable Trust, National Science Foundation, and Gustavus and Louise Pfeiffer Foundation. P.R.M. and T.R.C. are supported by fellowships from the Helen Hay Whitney Foundation and the National Institutes of Health (NRSA), respectively. W.G.D. is an investigator of the Howard Hughes Medical Institute.
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NIHUNSPECIFIED
Lucille P. Markey Charitable TrustUNSPECIFIED
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Gustavus and Louise Pfeiffer FoundationUNSPECIFIED
Howard Hughes Medical Institute (HHMI)UNSPECIFIED
Issue or Number:1
PubMed Central ID:PMC275819
Record Number:CaltechAUTHORS:MUEmbc95
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:MUEmbc95
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:3894
Collection:CaltechAUTHORS
Deposited By: Archive Administrator
Deposited On:18 Jul 2006
Last Modified:09 Mar 2020 13:18

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