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T Izumi and JL Maller
Department of Pharmacology, University of Colorado School of Medicine, Denver 80262.
The cdc25 phosphatase is a mitotic inducer that activates p34cdc2 at the G2/M transition by dephosphorylation of Tyr15 in p34cdc2. cdc25 itself is also regulated through periodic changes in its phosphorylation state. To elucidate the mechanism for induction of mitosis, phosphorylation of cdc25 has been investigated using recombinant proteins. cdc25 is phosphorylated by both cyclin A/p34cdc2 and cyclin B/p34cdc2 at similar sets of multiple sites in vitro. This phosphorylation retards its electrophoretical mobility and activates its ability to increase cyclin B/p34cdc2 kinase activity three- to fourfold in vitro, as found for endogenous Xenopus cdc25 in M-phase extracts. The threonine and serine residues followed by proline that are conserved between Xenopus and human cdc25 have been mutated. Both the triple mutation of Thr48, Thr67, and Thr138 and the quintuple mutation of these three threonine residues plus Ser205 and Ser285, almost completely abolish the shift in electrophoretic mobility of cdc25 after incubation with M-phase extracts or phosphorylation by p34cdc2. These mutations inhibit the activation of cdc25 by phosphorylation with p34cdc2 by 70 and 90%, respectively. At physiological concentrations these mutants cannot activate cyclin B/p34cdc2 in cdc25-immunodepleted oocyte extracts, suggesting that a positive feed-back loop between cdc2 and cdc25 is necessary for the full activation of cyclin B/p34cdc2 that induces abrupt entry into mitosis in vivo.
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
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|
|
|
|
|
|
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|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
P. Gowdy, H. Anderson, and M Roberge Entry into mitosis without Cdc2 kinase activation J. Cell Sci., January 11, 1998; 111(22): 3401 - 3410. [Abstract] [PDF]
|
|
|
|
|
|
C Lammer, S Wagerer, R Saffrich, D Mertens, W Ansorge, and I Hoffmann The cdc25B phosphatase is essential for the G2/M phase transition in human cells J. Cell Sci., January 8, 1998; 111(16): 2445 - 2453. [Abstract] [PDF]
|
|
|
|
|
|
A Abrieu, T Brassac, S Galas, D Fisher, J. Labbe, and M Doree The Polo-like kinase Plx1 is a component of the MPF amplification loop at the G2/M-phase transition of the cell cycle in Xenopus eggs J. Cell Sci., January 6, 1998; 111(12): 1751 - 1757. [Abstract] [PDF]
|
|
|
|
|
|
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|
|
|
|
|
|
R. Aligue, L. Wu, and P. Russell Regulation of Schizosaccharomyces pombe Wee1 Tyrosine Kinase J. Biol. Chem., May 16, 1997; 272(20): 13320 - 13325. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. R. Ernsting and J. E. Dixon The PPS1 Gene of Saccharomyces cerevisiae Codes for a Dual Specificity Protein Phosphatase with a Role in the DNA Synthesis Phase of the Cell Cycle J. Biol. Chem., April 4, 1997; 272(14): 9332 - 9343. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Borgne and L. Meijer Sequential Dephosphorylation of p34cdc2 on Thr-14 and Tyr-15 at the Prophase/Metaphase Transition J. Biol. Chem., November 1, 1996; 271(44): 27847 - 27854. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D Patra and W G Dunphy Xe-p9, a Xenopus Suc1/Cks homolog, has multiple essential roles in cell cycle control. Genes & Dev., June 15, 1996; 10(12): 1503 - 1515. [Abstract] [PDF]
|
|
|
|
|
|
J Creanor and J. Mitchison The kinetics of the B cyclin p56cdc13 and the phosphatase p80cdc25 during the cell cycle of the fission yeast Schizosaccharomyces pombe J. Cell Sci., January 6, 1996; 109(6): 1647 - 1653. [Abstract] [PDF]
|
|
|
|
 |
|
 S. Bissen Expression of the cell cycle control gene, cdc25, is constitutive in the segmental founder cells but is cell-cycle-regulated in the micromeres of leech embryos Development, January 9, 1995; 121(9): 3035 - 3043. [Abstract] [PDF]
|
|
|
|
|
|
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|
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|
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|
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