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. 1991 Nov;10(11):3297–3309. doi: 10.1002/j.1460-2075.1991.tb04894.x

Phosphorylation at Thr167 is required for Schizosaccharomyces pombe p34cdc2 function.

K L Gould 1, S Moreno 1, D J Owen 1, S Sazer 1, P Nurse 1
PMCID: PMC453056  PMID: 1655416

Abstract

Eukaryotic cell cycle progression requires the periodic activation and inactivation of a protein-serine/threonine kinase which in fission yeast is encoded by the cdc2+ gene. The activity of this gene product, p34cdc2, is controlled by numerous interactions with other proteins and by its phosphorylation state. In fission yeast, p34cdc2 is phosphorylated on two sites, one of which has been identified as Tyr15. Dephosphorylation of Tyr15 regulates the initiation of mitosis. To understand more completely the regulation of p34cdc2 kinase activity, we have identified the second site of phosphorylation as Thr167, a residue conserved amongst all p34cdc2 homologues. By analysing the phenotypes of cells expressing various position 167 mutations and performing in vitro experiments, we establish that Thr167 phosphorylation is required for p34cdc2 kinase activity at mitosis and is involved in the association of p34cdc2 with cyclin B. Dephosphorylation of Thr167 might also play a role in the exit from mitosis.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Anderson N. G., Maller J. L., Tonks N. K., Sturgill T. W. Requirement for integration of signals from two distinct phosphorylation pathways for activation of MAP kinase. Nature. 1990 Feb 15;343(6259):651–653. doi: 10.1038/343651a0. [DOI] [PubMed] [Google Scholar]
  2. Axton J. M., Dombrádi V., Cohen P. T., Glover D. M. One of the protein phosphatase 1 isoenzymes in Drosophila is essential for mitosis. Cell. 1990 Oct 5;63(1):33–46. doi: 10.1016/0092-8674(90)90286-n. [DOI] [PubMed] [Google Scholar]
  3. Blow J. J., Nurse P. A cdc2-like protein is involved in the initiation of DNA replication in Xenopus egg extracts. Cell. 1990 Sep 7;62(5):855–862. doi: 10.1016/0092-8674(90)90261-c. [DOI] [PubMed] [Google Scholar]
  4. Booher R. N., Alfa C. E., Hyams J. S., Beach D. H. The fission yeast cdc2/cdc13/suc1 protein kinase: regulation of catalytic activity and nuclear localization. Cell. 1989 Aug 11;58(3):485–497. doi: 10.1016/0092-8674(89)90429-7. [DOI] [PubMed] [Google Scholar]
  5. Booher R., Beach D. Interaction between cdc13+ and cdc2+ in the control of mitosis in fission yeast; dissociation of the G1 and G2 roles of the cdc2+ protein kinase. EMBO J. 1987 Nov;6(11):3441–3447. doi: 10.1002/j.1460-2075.1987.tb02667.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Booher R., Beach D. Involvement of a type 1 protein phosphatase encoded by bws1+ in fission yeast mitotic control. Cell. 1989 Jun 16;57(6):1009–1016. doi: 10.1016/0092-8674(89)90339-5. [DOI] [PubMed] [Google Scholar]
  7. Booher R., Beach D. Involvement of cdc13+ in mitotic control in Schizosaccharomyces pombe: possible interaction of the gene product with microtubules. EMBO J. 1988 Aug;7(8):2321–2327. doi: 10.1002/j.1460-2075.1988.tb03075.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Booher R., Beach D. Site-specific mutagenesis of cdc2+, a cell cycle control gene of the fission yeast Schizosaccharomyces pombe. Mol Cell Biol. 1986 Oct;6(10):3523–3530. doi: 10.1128/mcb.6.10.3523. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Boulton T. G., Yancopoulos G. D., Gregory J. S., Slaughter C., Moomaw C., Hsu J., Cobb M. H. An insulin-stimulated protein kinase similar to yeast kinases involved in cell cycle control. Science. 1990 Jul 6;249(4964):64–67. doi: 10.1126/science.2164259. [DOI] [PubMed] [Google Scholar]
  10. Brizuela L., Draetta G., Beach D. p13suc1 acts in the fission yeast cell division cycle as a component of the p34cdc2 protein kinase. EMBO J. 1987 Nov;6(11):3507–3514. doi: 10.1002/j.1460-2075.1987.tb02676.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Cisek L. J., Corden J. L. Phosphorylation of RNA polymerase by the murine homologue of the cell-cycle control protein cdc2. Nature. 1989 Jun 29;339(6227):679–684. doi: 10.1038/339679a0. [DOI] [PubMed] [Google Scholar]
  12. Cooper J. A., Sefton B. M., Hunter T. Detection and quantification of phosphotyrosine in proteins. Methods Enzymol. 1983;99:387–402. doi: 10.1016/0076-6879(83)99075-4. [DOI] [PubMed] [Google Scholar]
  13. Cross F. R. DAF1, a mutant gene affecting size control, pheromone arrest, and cell cycle kinetics of Saccharomyces cerevisiae. Mol Cell Biol. 1988 Nov;8(11):4675–4684. doi: 10.1128/mcb.8.11.4675. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. D'Urso G., Marraccino R. L., Marshak D. R., Roberts J. M. Cell cycle control of DNA replication by a homologue from human cells of the p34cdc2 protein kinase. Science. 1990 Nov 9;250(4982):786–791. doi: 10.1126/science.2173140. [DOI] [PubMed] [Google Scholar]
  15. Dasso M., Newport J. W. Completion of DNA replication is monitored by a feedback system that controls the initiation of mitosis in vitro: studies in Xenopus. Cell. 1990 Jun 1;61(5):811–823. doi: 10.1016/0092-8674(90)90191-g. [DOI] [PubMed] [Google Scholar]
  16. Dean A. M., Koshland D. E., Jr Electrostatic and steric contributions to regulation at the active site of isocitrate dehydrogenase. Science. 1990 Aug 31;249(4972):1044–1046. doi: 10.1126/science.2204110. [DOI] [PubMed] [Google Scholar]
  17. Doonan J. H., Morris N. R. The bimG gene of Aspergillus nidulans, required for completion of anaphase, encodes a homolog of mammalian phosphoprotein phosphatase 1. Cell. 1989 Jun 16;57(6):987–996. doi: 10.1016/0092-8674(89)90337-1. [DOI] [PubMed] [Google Scholar]
  18. Draetta G., Beach D. Activation of cdc2 protein kinase during mitosis in human cells: cell cycle-dependent phosphorylation and subunit rearrangement. Cell. 1988 Jul 1;54(1):17–26. doi: 10.1016/0092-8674(88)90175-4. [DOI] [PubMed] [Google Scholar]
  19. Draetta G., Brizuela L., Potashkin J., Beach D. Identification of p34 and p13, human homologs of the cell cycle regulators of fission yeast encoded by cdc2+ and suc1+. Cell. 1987 Jul 17;50(2):319–325. doi: 10.1016/0092-8674(87)90227-3. [DOI] [PubMed] [Google Scholar]
  20. Draetta G. Cell cycle control in eukaryotes: molecular mechanisms of cdc2 activation. Trends Biochem Sci. 1990 Oct;15(10):378–383. doi: 10.1016/0968-0004(90)90235-4. [DOI] [PubMed] [Google Scholar]
  21. Draetta G., Luca F., Westendorf J., Brizuela L., Ruderman J., Beach D. Cdc2 protein kinase is complexed with both cyclin A and B: evidence for proteolytic inactivation of MPF. Cell. 1989 Mar 10;56(5):829–838. doi: 10.1016/0092-8674(89)90687-9. [DOI] [PubMed] [Google Scholar]
  22. Ducommun B., Draetta G., Young P., Beach D. Fission yeast cdc25 is a cell-cycle regulated protein. Biochem Biophys Res Commun. 1990 Feb 28;167(1):301–309. doi: 10.1016/0006-291x(90)91765-k. [DOI] [PubMed] [Google Scholar]
  23. Dunphy W. G., Brizuela L., Beach D., Newport J. The Xenopus cdc2 protein is a component of MPF, a cytoplasmic regulator of mitosis. Cell. 1988 Jul 29;54(3):423–431. doi: 10.1016/0092-8674(88)90205-x. [DOI] [PubMed] [Google Scholar]
  24. Dunphy W. G., Newport J. W. Fission yeast p13 blocks mitotic activation and tyrosine dephosphorylation of the Xenopus cdc2 protein kinase. Cell. 1989 Jul 14;58(1):181–191. doi: 10.1016/0092-8674(89)90414-5. [DOI] [PubMed] [Google Scholar]
  25. Featherstone C., Russell P. Fission yeast p107wee1 mitotic inhibitor is a tyrosine/serine kinase. Nature. 1991 Feb 28;349(6312):808–811. doi: 10.1038/349808a0. [DOI] [PubMed] [Google Scholar]
  26. Felix M. A., Pines J., Hunt T., Karsenti E. A post-ribosomal supernatant from activated Xenopus eggs that displays post-translationally regulated oscillation of its cdc2+ mitotic kinase activity. EMBO J. 1989 Oct;8(10):3059–3069. doi: 10.1002/j.1460-2075.1989.tb08457.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Fleig U. N., Nurse P. Expression of a dominant negative allele of cdc2 prevents activation of the endogenous p34cdc2 kinase. Mol Gen Genet. 1991 May;226(3):432–440. doi: 10.1007/BF00260656. [DOI] [PubMed] [Google Scholar]
  28. Freeman R. S., Donoghue D. J. Protein kinases and protooncogenes: biochemical regulators of the eukaryotic cell cycle. Biochemistry. 1991 Mar 5;30(9):2293–2302. doi: 10.1021/bi00223a001. [DOI] [PubMed] [Google Scholar]
  29. Furukawa Y., Piwnica-Worms H., Ernst T. J., Kanakura Y., Griffin J. D. cdc2 gene expression at the G1 to S transition in human T lymphocytes. Science. 1990 Nov 9;250(4982):805–808. doi: 10.1126/science.2237430. [DOI] [PubMed] [Google Scholar]
  30. Félix M. A., Cohen P., Karsenti E. Cdc2 H1 kinase is negatively regulated by a type 2A phosphatase in the Xenopus early embryonic cell cycle: evidence from the effects of okadaic acid. EMBO J. 1990 Mar;9(3):675–683. doi: 10.1002/j.1460-2075.1990.tb08159.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Gautier J., Maller J. L. Cyclin B in Xenopus oocytes: implications for the mechanism of pre-MPF activation. EMBO J. 1991 Jan;10(1):177–182. doi: 10.1002/j.1460-2075.1991.tb07934.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Gautier J., Matsukawa T., Nurse P., Maller J. Dephosphorylation and activation of Xenopus p34cdc2 protein kinase during the cell cycle. Nature. 1989 Jun 22;339(6226):626–629. doi: 10.1038/339626a0. [DOI] [PubMed] [Google Scholar]
  33. Gautier J., Minshull J., Lohka M., Glotzer M., Hunt T., Maller J. L. Cyclin is a component of maturation-promoting factor from Xenopus. Cell. 1990 Feb 9;60(3):487–494. doi: 10.1016/0092-8674(90)90599-a. [DOI] [PubMed] [Google Scholar]
  34. Gautier J., Norbury C., Lohka M., Nurse P., Maller J. Purified maturation-promoting factor contains the product of a Xenopus homolog of the fission yeast cell cycle control gene cdc2+. Cell. 1988 Jul 29;54(3):433–439. doi: 10.1016/0092-8674(88)90206-1. [DOI] [PubMed] [Google Scholar]
  35. Ghiara J. B., Richardson H. E., Sugimoto K., Henze M., Lew D. J., Wittenberg C., Reed S. I. A cyclin B homolog in S. cerevisiae: chronic activation of the Cdc28 protein kinase by cyclin prevents exit from mitosis. Cell. 1991 Apr 5;65(1):163–174. doi: 10.1016/0092-8674(91)90417-w. [DOI] [PubMed] [Google Scholar]
  36. Goris J., Hermann J., Hendrix P., Ozon R., Merlevede W. Okadaic acid, a specific protein phosphatase inhibitor, induces maturation and MPF formation in Xenopus laevis oocytes. FEBS Lett. 1989 Mar 13;245(1-2):91–94. doi: 10.1016/0014-5793(89)80198-x. [DOI] [PubMed] [Google Scholar]
  37. Gould K. L., Moreno S., Tonks N. K., Nurse P. Complementation of the mitotic activator, p80cdc25, by a human protein-tyrosine phosphatase. Science. 1990 Dec 14;250(4987):1573–1576. doi: 10.1126/science.1703321. [DOI] [PubMed] [Google Scholar]
  38. Gould K. L., Nurse P. Tyrosine phosphorylation of the fission yeast cdc2+ protein kinase regulates entry into mitosis. Nature. 1989 Nov 2;342(6245):39–45. doi: 10.1038/342039a0. [DOI] [PubMed] [Google Scholar]
  39. Hadwiger J. A., Wittenberg C., Richardson H. E., de Barros Lopes M., Reed S. I. A family of cyclin homologs that control the G1 phase in yeast. Proc Natl Acad Sci U S A. 1989 Aug;86(16):6255–6259. doi: 10.1073/pnas.86.16.6255. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Hagan I., Hayles J., Nurse P. Cloning and sequencing of the cyclin-related cdc13+ gene and a cytological study of its role in fission yeast mitosis. J Cell Sci. 1988 Dec;91(Pt 4):587–595. doi: 10.1242/jcs.91.4.587. [DOI] [PubMed] [Google Scholar]
  41. Hindley J., Phear G. A. Sequence of the cell division gene CDC2 from Schizosaccharomyces pombe; patterns of splicing and homology to protein kinases. Gene. 1984 Nov;31(1-3):129–134. doi: 10.1016/0378-1119(84)90203-8. [DOI] [PubMed] [Google Scholar]
  42. Hirt H., Páy A., Györgyey J., Bakó L., Németh K., Bögre L., Schweyen R. J., Heberle-Bors E., Dudits D. Complementation of a yeast cell cycle mutant by an alfalfa cDNA encoding a protein kinase homologous to p34cdc2. Proc Natl Acad Sci U S A. 1991 Mar 1;88(5):1636–1640. doi: 10.1073/pnas.88.5.1636. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Hurley J. H., Dean A. M., Sohl J. L., Koshland D. E., Jr, Stroud R. M. Regulation of an enzyme by phosphorylation at the active site. Science. 1990 Aug 31;249(4972):1012–1016. doi: 10.1126/science.2204109. [DOI] [PubMed] [Google Scholar]
  44. Jessus C., Ducommun B., Beach D. Direct activation of cdc2 with phosphatase: identification of p13suc1-sensitive and insensitive steps. FEBS Lett. 1990 Jun 18;266(1-2):4–8. doi: 10.1016/0014-5793(90)90002-c. [DOI] [PubMed] [Google Scholar]
  45. Jimenez J., Alphey L., Nurse P., Glover D. M. Complementation of fission yeast cdc2ts and cdc25ts mutants identifies two cell cycle genes from Drosophila: a cdc2 homologue and string. EMBO J. 1990 Nov;9(11):3565–3571. doi: 10.1002/j.1460-2075.1990.tb07567.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Kamps M. P., Sefton B. M. Acid and base hydrolysis of phosphoproteins bound to immobilon facilitates analysis of phosphoamino acids in gel-fractionated proteins. Anal Biochem. 1989 Jan;176(1):22–27. doi: 10.1016/0003-2697(89)90266-2. [DOI] [PubMed] [Google Scholar]
  47. Kinoshita N., Ohkura H., Yanagida M. Distinct, essential roles of type 1 and 2A protein phosphatases in the control of the fission yeast cell division cycle. Cell. 1990 Oct 19;63(2):405–415. doi: 10.1016/0092-8674(90)90173-c. [DOI] [PubMed] [Google Scholar]
  48. Krek W., Nigg E. A. Differential phosphorylation of vertebrate p34cdc2 kinase at the G1/S and G2/M transitions of the cell cycle: identification of major phosphorylation sites. EMBO J. 1991 Feb;10(2):305–316. doi: 10.1002/j.1460-2075.1991.tb07951.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. Krek W., Nigg E. A. Structure and developmental expression of the chicken CDC2 kinase. EMBO J. 1989 Oct;8(10):3071–3078. doi: 10.1002/j.1460-2075.1989.tb08458.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. Kumagai A., Dunphy W. G. The cdc25 protein controls tyrosine dephosphorylation of the cdc2 protein in a cell-free system. Cell. 1991 Mar 8;64(5):903–914. doi: 10.1016/0092-8674(91)90315-p. [DOI] [PubMed] [Google Scholar]
  51. Labbe J. C., Lee M. G., Nurse P., Picard A., Doree M. Activation at M-phase of a protein kinase encoded by a starfish homologue of the cell cycle control gene cdc2+. Nature. 1988 Sep 15;335(6187):251–254. doi: 10.1038/335251a0. [DOI] [PubMed] [Google Scholar]
  52. Labbe J. C., Picard A., Peaucellier G., Cavadore J. C., Nurse P., Doree M. Purification of MPF from starfish: identification as the H1 histone kinase p34cdc2 and a possible mechanism for its periodic activation. Cell. 1989 Apr 21;57(2):253–263. doi: 10.1016/0092-8674(89)90963-x. [DOI] [PubMed] [Google Scholar]
  53. Labbé J. C., Capony J. P., Caput D., Cavadore J. C., Derancourt J., Kaghad M., Lelias J. M., Picard A., Dorée M. MPF from starfish oocytes at first meiotic metaphase is a heterodimer containing one molecule of cdc2 and one molecule of cyclin B. EMBO J. 1989 Oct;8(10):3053–3058. doi: 10.1002/j.1460-2075.1989.tb08456.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  54. Lee M. G., Norbury C. J., Spurr N. K., Nurse P. Regulated expression and phosphorylation of a possible mammalian cell-cycle control protein. Nature. 1988 Jun 16;333(6174):676–679. doi: 10.1038/333676a0. [DOI] [PubMed] [Google Scholar]
  55. Lee M. G., Nurse P. Complementation used to clone a human homologue of the fission yeast cell cycle control gene cdc2. Nature. 1987 May 7;327(6117):31–35. doi: 10.1038/327031a0. [DOI] [PubMed] [Google Scholar]
  56. Lee T. H., Solomon M. J., Mumby M. C., Kirschner M. W. INH, a negative regulator of MPF, is a form of protein phosphatase 2A. Cell. 1991 Jan 25;64(2):415–423. doi: 10.1016/0092-8674(91)90649-j. [DOI] [PubMed] [Google Scholar]
  57. Lehner C. F., O'Farrell P. H. Drosophila cdc2 homologs: a functional homolog is coexpressed with a cognate variant. EMBO J. 1990 Nov;9(11):3573–3581. doi: 10.1002/j.1460-2075.1990.tb07568.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  58. Levin L. R., Zoller M. J. Association of catalytic and regulatory subunits of cyclic AMP-dependent protein kinase requires a negatively charged side group at a conserved threonine. Mol Cell Biol. 1990 Mar;10(3):1066–1075. doi: 10.1128/mcb.10.3.1066. [DOI] [PMC free article] [PubMed] [Google Scholar]
  59. Lewin B. Driving the cell cycle: M phase kinase, its partners, and substrates. Cell. 1990 Jun 1;61(5):743–752. doi: 10.1016/0092-8674(90)90181-d. [DOI] [PubMed] [Google Scholar]
  60. Lohka M. J. Mitotic control by metaphase-promoting factor and cdc proteins. J Cell Sci. 1989 Feb;92(Pt 2):131–135. doi: 10.1242/jcs.92.2.131. [DOI] [PubMed] [Google Scholar]
  61. Lundgren K., Walworth N., Booher R., Dembski M., Kirschner M., Beach D. mik1 and wee1 cooperate in the inhibitory tyrosine phosphorylation of cdc2. Cell. 1991 Mar 22;64(6):1111–1122. doi: 10.1016/0092-8674(91)90266-2. [DOI] [PubMed] [Google Scholar]
  62. Lörincz A. T., Reed S. I. Primary structure homology between the product of yeast cell division control gene CDC28 and vertebrate oncogenes. Nature. 1984 Jan 12;307(5947):183–185. doi: 10.1038/307183a0. [DOI] [PubMed] [Google Scholar]
  63. Maundrell K. nmt1 of fission yeast. A highly transcribed gene completely repressed by thiamine. J Biol Chem. 1990 Jul 5;265(19):10857–10864. [PubMed] [Google Scholar]
  64. Meijer L., Arion D., Golsteyn R., Pines J., Brizuela L., Hunt T., Beach D. Cyclin is a component of the sea urchin egg M-phase specific histone H1 kinase. EMBO J. 1989 Aug;8(8):2275–2282. doi: 10.1002/j.1460-2075.1989.tb08353.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  65. Mendenhall M. D., Jones C. A., Reed S. I. Dual regulation of the yeast CDC28-p40 protein kinase complex: cell cycle, pheromone, and nutrient limitation effects. Cell. 1987 Sep 11;50(6):927–935. doi: 10.1016/0092-8674(87)90519-8. [DOI] [PubMed] [Google Scholar]
  66. Mendenhall M. D., Richardson H. E., Reed S. I. Dominant negative protein kinase mutations that confer a G1 arrest phenotype. Proc Natl Acad Sci U S A. 1988 Jun;85(12):4426–4430. doi: 10.1073/pnas.85.12.4426. [DOI] [PMC free article] [PubMed] [Google Scholar]
  67. Moreno S., Hayles J., Nurse P. Regulation of p34cdc2 protein kinase during mitosis. Cell. 1989 Jul 28;58(2):361–372. doi: 10.1016/0092-8674(89)90850-7. [DOI] [PubMed] [Google Scholar]
  68. Moreno S., Klar A., Nurse P. Molecular genetic analysis of fission yeast Schizosaccharomyces pombe. Methods Enzymol. 1991;194:795–823. doi: 10.1016/0076-6879(91)94059-l. [DOI] [PubMed] [Google Scholar]
  69. Moreno S., Nurse P., Russell P. Regulation of mitosis by cyclic accumulation of p80cdc25 mitotic inducer in fission yeast. Nature. 1990 Apr 5;344(6266):549–552. doi: 10.1038/344549a0. [DOI] [PubMed] [Google Scholar]
  70. Morla A. O., Draetta G., Beach D., Wang J. Y. Reversible tyrosine phosphorylation of cdc2: dephosphorylation accompanies activation during entry into mitosis. Cell. 1989 Jul 14;58(1):193–203. doi: 10.1016/0092-8674(89)90415-7. [DOI] [PubMed] [Google Scholar]
  71. Murray A. W., Kirschner M. W. Dominoes and clocks: the union of two views of the cell cycle. Science. 1989 Nov 3;246(4930):614–621. doi: 10.1126/science.2683077. [DOI] [PubMed] [Google Scholar]
  72. Nash R., Tokiwa G., Anand S., Erickson K., Futcher A. B. The WHI1+ gene of Saccharomyces cerevisiae tethers cell division to cell size and is a cyclin homolog. EMBO J. 1988 Dec 20;7(13):4335–4346. doi: 10.1002/j.1460-2075.1988.tb03332.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  73. Norbury C., Blow J., Nurse P. Regulatory phosphorylation of the p34cdc2 protein kinase in vertebrates. EMBO J. 1991 Nov;10(11):3321–3329. doi: 10.1002/j.1460-2075.1991.tb04896.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  74. Nurse P., Bissett Y. Gene required in G1 for commitment to cell cycle and in G2 for control of mitosis in fission yeast. Nature. 1981 Aug 6;292(5823):558–560. doi: 10.1038/292558a0. [DOI] [PubMed] [Google Scholar]
  75. Nurse P. Universal control mechanism regulating onset of M-phase. Nature. 1990 Apr 5;344(6266):503–508. doi: 10.1038/344503a0. [DOI] [PubMed] [Google Scholar]
  76. Ohkura H., Kinoshita N., Miyatani S., Toda T., Yanagida M. The fission yeast dis2+ gene required for chromosome disjoining encodes one of two putative type 1 protein phosphatases. Cell. 1989 Jun 16;57(6):997–1007. doi: 10.1016/0092-8674(89)90338-3. [DOI] [PubMed] [Google Scholar]
  77. Payne D. M., Rossomando A. J., Martino P., Erickson A. K., Her J. H., Shabanowitz J., Hunt D. F., Weber M. J., Sturgill T. W. Identification of the regulatory phosphorylation sites in pp42/mitogen-activated protein kinase (MAP kinase). EMBO J. 1991 Apr;10(4):885–892. doi: 10.1002/j.1460-2075.1991.tb08021.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  78. Picard A., Capony J. P., Brautigan D. L., Dorée M. Involvement of protein phosphatases 1 and 2A in the control of M phase-promoting factor activity in starfish. J Cell Biol. 1989 Dec;109(6 Pt 2):3347–3354. doi: 10.1083/jcb.109.6.3347. [DOI] [PMC free article] [PubMed] [Google Scholar]
  79. Piggott J. R., Rai R., Carter B. L. A bifunctional gene product involved in two phases of the yeast cell cycle. Nature. 1982 Jul 22;298(5872):391–393. doi: 10.1038/298391a0. [DOI] [PubMed] [Google Scholar]
  80. Pines J., Hunter T. Isolation of a human cyclin cDNA: evidence for cyclin mRNA and protein regulation in the cell cycle and for interaction with p34cdc2. Cell. 1989 Sep 8;58(5):833–846. doi: 10.1016/0092-8674(89)90936-7. [DOI] [PubMed] [Google Scholar]
  81. Pines J., Hunter T. p34cdc2: the S and M kinase? New Biol. 1990 May;2(5):389–401. [PubMed] [Google Scholar]
  82. Pondaven P., Meijer L., Beach D. Activation of M-phase-specific histone H1 kinase by modification of the phosphorylation of its p34cdc2 and cyclin components. Genes Dev. 1990 Jan;4(1):9–17. doi: 10.1101/gad.4.1.9. [DOI] [PubMed] [Google Scholar]
  83. Reed S. I., Wittenberg C. Mitotic role for the Cdc28 protein kinase of Saccharomyces cerevisiae. Proc Natl Acad Sci U S A. 1990 Aug;87(15):5697–5701. doi: 10.1073/pnas.87.15.5697. [DOI] [PMC free article] [PubMed] [Google Scholar]
  84. Richardson H. E., Wittenberg C., Cross F., Reed S. I. An essential G1 function for cyclin-like proteins in yeast. Cell. 1989 Dec 22;59(6):1127–1133. doi: 10.1016/0092-8674(89)90768-x. [DOI] [PubMed] [Google Scholar]
  85. Russell P., Nurse P. Negative regulation of mitosis by wee1+, a gene encoding a protein kinase homolog. Cell. 1987 May 22;49(4):559–567. doi: 10.1016/0092-8674(87)90458-2. [DOI] [PubMed] [Google Scholar]
  86. Russell P., Nurse P. cdc25+ functions as an inducer in the mitotic control of fission yeast. Cell. 1986 Apr 11;45(1):145–153. doi: 10.1016/0092-8674(86)90546-5. [DOI] [PubMed] [Google Scholar]
  87. Sazer S., Sherwood S. W. Mitochondrial growth and DNA synthesis occur in the absence of nuclear DNA replication in fission yeast. J Cell Sci. 1990 Nov;97(Pt 3):509–516. doi: 10.1242/jcs.97.3.509. [DOI] [PubMed] [Google Scholar]
  88. Simanis V., Nurse P. The cell cycle control gene cdc2+ of fission yeast encodes a protein kinase potentially regulated by phosphorylation. Cell. 1986 Apr 25;45(2):261–268. doi: 10.1016/0092-8674(86)90390-9. [DOI] [PubMed] [Google Scholar]
  89. Solomon M. J., Glotzer M., Lee T. H., Philippe M., Kirschner M. W. Cyclin activation of p34cdc2. Cell. 1990 Nov 30;63(5):1013–1024. doi: 10.1016/0092-8674(90)90504-8. [DOI] [PubMed] [Google Scholar]
  90. Spurr N. K., Gough A. C., Lee M. G. Cloning of the mouse homologue of the yeast cell cycle control gene cdc2. DNA Seq. 1990;1(1):49–54. doi: 10.3109/10425179009041346. [DOI] [PubMed] [Google Scholar]
  91. Surana U., Robitsch H., Price C., Schuster T., Fitch I., Futcher A. B., Nasmyth K. The role of CDC28 and cyclins during mitosis in the budding yeast S. cerevisiae. Cell. 1991 Apr 5;65(1):145–161. doi: 10.1016/0092-8674(91)90416-v. [DOI] [PubMed] [Google Scholar]
  92. Th'ng J. P., Wright P. S., Hamaguchi J., Lee M. G., Norbury C. J., Nurse P., Bradbury E. M. The FT210 cell line is a mouse G2 phase mutant with a temperature-sensitive CDC2 gene product. Cell. 1990 Oct 19;63(2):313–324. doi: 10.1016/0092-8674(90)90164-a. [DOI] [PubMed] [Google Scholar]
  93. Thorsness P. E., Koshland D. E., Jr Inactivation of isocitrate dehydrogenase by phosphorylation is mediated by the negative charge of the phosphate. J Biol Chem. 1987 Aug 5;262(22):10422–10425. [PubMed] [Google Scholar]
  94. Wittenberg C., Sugimoto K., Reed S. I. G1-specific cyclins of S. cerevisiae: cell cycle periodicity, regulation by mating pheromone, and association with the p34CDC28 protein kinase. Cell. 1990 Jul 27;62(2):225–237. doi: 10.1016/0092-8674(90)90361-h. [DOI] [PubMed] [Google Scholar]
  95. Yamashita K., Yasuda H., Pines J., Yasumoto K., Nishitani H., Ohtsubo M., Hunter T., Sugimura T., Nishimoto T. Okadaic acid, a potent inhibitor of type 1 and type 2A protein phosphatases, activates cdc2/H1 kinase and transiently induces a premature mitosis-like state in BHK21 cells. EMBO J. 1990 Dec;9(13):4331–4338. doi: 10.1002/j.1460-2075.1990.tb07882.x. [DOI] [PMC free article] [PubMed] [Google Scholar]

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