Regulation of the human WEE1Hu CDK tyrosine 15-kinase during the cell cycle (original) (raw)

Abstract

In higher eukaryotes, the cyclin-dependent kinases (CDKs) are negatively regulated by phosphorylation on threonine 14 (T14) and tyrosine 15 (Y15). In fission yeast, the Wee1 and mitosis inhibitory kinase 1 (Mik1) protein kinases phosphorylate Y15 in Cdc2. WEE1Hu is the only known protein kinase that can carry out this inhibitory phosphorylation on Y15 in higher eukaryotes. In the present study, we examined the endogenous products of WEE1Hu in human cells and found that the original WEE1Hu cDNA lacked 214 amino acids at the N-terminus. The predicted full-length protein has weak, but significant, similarity over its entire length with Mik1. Thus, we suggest that 'WEE1Hu' is a Mik1-related protein rather than a Wee1 homologue. When isolated in immunoprecipitates, the endogenous WEE1Hu phosphorylated several cyclin-associated CDKs on Y15. WEE1Hu activity increased during S and G2 phases in parallel with the level of protein. Its activity decreased at M phase when WEE1Hu became transiently hyperphosphorylated. In addition, a decrease in WEE1Hu protein level was observed at M/G1 phase. Apparently, the hyperphosphorylation and degradation in combination caused inactivation of WEE1Hu at M phase and the following G1 phase. These results suggest that the activity of WEE1Hu is regulated by phosphorylation and proteolytic degradation, and that WEE1Hu plays a role in inhibiting mitosis before M phase by phosphorylating cyclin B1-Cdc2.

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  1. Atherton-Fessler S., Liu F., Gabrielli B., Lee M. S., Peng C. Y., Piwnica-Worms H. Cell cycle regulation of the p34cdc2 inhibitory kinases. Mol Biol Cell. 1994 Sep;5(9):989–1001. doi: 10.1091/mbc.5.9.989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. 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]
  3. Booher R. N., Deshaies R. J., Kirschner M. W. Properties of Saccharomyces cerevisiae wee1 and its differential regulation of p34CDC28 in response to G1 and G2 cyclins. EMBO J. 1993 Sep;12(9):3417–3426. doi: 10.1002/j.1460-2075.1993.tb06016.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Boyle W. J., van der Geer P., Hunter T. Phosphopeptide mapping and phosphoamino acid analysis by two-dimensional separation on thin-layer cellulose plates. Methods Enzymol. 1991;201:110–149. doi: 10.1016/0076-6879(91)01013-r. [DOI] [PubMed] [Google Scholar]
  5. Chomczynski P., Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987 Apr;162(1):156–159. doi: 10.1006/abio.1987.9999. [DOI] [PubMed] [Google Scholar]
  6. Cleveland D. W., Fischer S. G., Kirschner M. W., Laemmli U. K. Peptide mapping by limited proteolysis in sodium dodecyl sulfate and analysis by gel electrophoresis. J Biol Chem. 1977 Feb 10;252(3):1102–1106. [PubMed] [Google Scholar]
  7. Coleman T. R., Tang Z., Dunphy W. G. Negative regulation of the wee1 protein kinase by direct action of the nim1/cdr1 mitotic inducer. Cell. 1993 Mar 26;72(6):919–929. doi: 10.1016/0092-8674(93)90580-j. [DOI] [PubMed] [Google Scholar]
  8. 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]
  9. Fantes P. Epistatic gene interactions in the control of division in fission yeast. Nature. 1979 May 31;279(5712):428–430. doi: 10.1038/279428a0. [DOI] [PubMed] [Google Scholar]
  10. 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]
  11. Feilotter H., Nurse P., Young P. G. Genetic and molecular analysis of cdr1/nim1 in Schizosaccharomyces pombe. Genetics. 1991 Feb;127(2):309–318. doi: 10.1093/genetics/127.2.309. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Feng G. S., Chong K., Kumar A., Williams B. R. Identification of double-stranded RNA-binding domains in the interferon-induced double-stranded RNA-activated p68 kinase. Proc Natl Acad Sci U S A. 1992 Jun 15;89(12):5447–5451. doi: 10.1073/pnas.89.12.5447. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Galaktionov K., Beach D. Specific activation of cdc25 tyrosine phosphatases by B-type cyclins: evidence for multiple roles of mitotic cyclins. Cell. 1991 Dec 20;67(6):1181–1194. doi: 10.1016/0092-8674(91)90294-9. [DOI] [PubMed] [Google Scholar]
  14. Gautier J., Solomon M. J., Booher R. N., Bazan J. F., Kirschner M. W. cdc25 is a specific tyrosine phosphatase that directly activates p34cdc2. Cell. 1991 Oct 4;67(1):197–211. doi: 10.1016/0092-8674(91)90583-k. [DOI] [PubMed] [Google Scholar]
  15. Giordano A., Whyte P., Harlow E., Franza B. R., Jr, Beach D., Draetta G. A 60 kd cdc2-associated polypeptide complexes with the E1A proteins in adenovirus-infected cells. Cell. 1989 Sep 8;58(5):981–990. doi: 10.1016/0092-8674(89)90949-5. [DOI] [PubMed] [Google Scholar]
  16. Glotzer M., Murray A. W., Kirschner M. W. Cyclin is degraded by the ubiquitin pathway. Nature. 1991 Jan 10;349(6305):132–138. doi: 10.1038/349132a0. [DOI] [PubMed] [Google Scholar]
  17. 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]
  18. Gu Y., Rosenblatt J., Morgan D. O. Cell cycle regulation of CDK2 activity by phosphorylation of Thr160 and Tyr15. EMBO J. 1992 Nov;11(11):3995–4005. doi: 10.1002/j.1460-2075.1992.tb05493.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Hanks S. K. Homology probing: identification of cDNA clones encoding members of the protein-serine kinase family. Proc Natl Acad Sci U S A. 1987 Jan;84(2):388–392. doi: 10.1073/pnas.84.2.388. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Heald R., McLoughlin M., McKeon F. Human wee1 maintains mitotic timing by protecting the nucleus from cytoplasmically activated Cdc2 kinase. Cell. 1993 Aug 13;74(3):463–474. doi: 10.1016/0092-8674(93)80048-j. [DOI] [PubMed] [Google Scholar]
  21. Heintz N., Sive H. L., Roeder R. G. Regulation of human histone gene expression: kinetics of accumulation and changes in the rate of synthesis and in the half-lives of individual histone mRNAs during the HeLa cell cycle. Mol Cell Biol. 1983 Apr;3(4):539–550. doi: 10.1128/mcb.3.4.539. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Her J. H., Lakhani S., Zu K., Vila J., Dent P., Sturgill T. W., Weber M. J. Dual phosphorylation and autophosphorylation in mitogen-activated protein (MAP) kinase activation. Biochem J. 1993 Nov 15;296(Pt 1):25–31. doi: 10.1042/bj2960025. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Hoffmann I., Clarke P. R., Marcote M. J., Karsenti E., Draetta G. Phosphorylation and activation of human cdc25-C by cdc2--cyclin B and its involvement in the self-amplification of MPF at mitosis. EMBO J. 1993 Jan;12(1):53–63. doi: 10.1002/j.1460-2075.1993.tb05631.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Honda R., Ohba Y., Nagata A., Okayama H., Yasuda H. Dephosphorylation of human p34cdc2 kinase on both Thr-14 and Tyr-15 by human cdc25B phosphatase. FEBS Lett. 1993 Mar 8;318(3):331–334. doi: 10.1016/0014-5793(93)80540-b. [DOI] [PubMed] [Google Scholar]
  25. Honda R., Ohba Y., Yasuda H. The cell cycle regulator, human p50weel, is a tyrosine kinase and not a serine/tyrosine kinase. Biochem Biophys Res Commun. 1992 Aug 14;186(3):1333–1338. doi: 10.1016/s0006-291x(05)81552-9. [DOI] [PubMed] [Google Scholar]
  26. Hunter T. Braking the cycle. Cell. 1993 Dec 3;75(5):839–841. doi: 10.1016/0092-8674(93)90528-x. [DOI] [PubMed] [Google Scholar]
  27. Igarashi M., Nagata A., Jinno S., Suto K., Okayama H. Wee1(+)-like gene in human cells. Nature. 1991 Sep 5;353(6339):80–83. doi: 10.1038/353080a0. [DOI] [PubMed] [Google Scholar]
  28. Izumi T., Walker D. H., Maller J. L. Periodic changes in phosphorylation of the Xenopus cdc25 phosphatase regulate its activity. Mol Biol Cell. 1992 Aug;3(8):927–939. doi: 10.1091/mbc.3.8.927. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Kato J. Y., Matsuoka M., Strom D. K., Sherr C. J. Regulation of cyclin D-dependent kinase 4 (cdk4) by cdk4-activating kinase. Mol Cell Biol. 1994 Apr;14(4):2713–2721. doi: 10.1128/mcb.14.4.2713. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Koff A., Cross F., Fisher A., Schumacher J., Leguellec K., Philippe M., Roberts J. M. Human cyclin E, a new cyclin that interacts with two members of the CDC2 gene family. Cell. 1991 Sep 20;66(6):1217–1228. doi: 10.1016/0092-8674(91)90044-y. [DOI] [PubMed] [Google Scholar]
  31. Koff A., Giordano A., Desai D., Yamashita K., Harper J. W., Elledge S., Nishimoto T., Morgan D. O., Franza B. R., Roberts J. M. Formation and activation of a cyclin E-cdk2 complex during the G1 phase of the human cell cycle. Science. 1992 Sep 18;257(5077):1689–1694. doi: 10.1126/science.1388288. [DOI] [PubMed] [Google Scholar]
  32. Kornbluth S., Sebastian B., Hunter T., Newport J. Membrane localization of the kinase which phosphorylates p34cdc2 on threonine 14. Mol Biol Cell. 1994 Mar;5(3):273–282. doi: 10.1091/mbc.5.3.273. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Kozak M. An analysis of vertebrate mRNA sequences: intimations of translational control. J Cell Biol. 1991 Nov;115(4):887–903. doi: 10.1083/jcb.115.4.887. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Krek W., Nigg E. A. Mutations of p34cdc2 phosphorylation sites induce premature mitotic events in HeLa cells: evidence for a double block to p34cdc2 kinase activation in vertebrates. EMBO J. 1991 Nov;10(11):3331–3341. doi: 10.1002/j.1460-2075.1991.tb04897.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Kuang J., Ashorn C. L., Gonzalez-Kuyvenhoven M., Penkala J. E. cdc25 is one of the MPM-2 antigens involved in the activation of maturation-promoting factor. Mol Biol Cell. 1994 Feb;5(2):135–145. doi: 10.1091/mbc.5.2.135. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Kumagai A., Dunphy W. G. Regulation of the cdc25 protein during the cell cycle in Xenopus extracts. Cell. 1992 Jul 10;70(1):139–151. doi: 10.1016/0092-8674(92)90540-s. [DOI] [PubMed] [Google Scholar]
  37. 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]
  38. Kunkel T. A. Rapid and efficient site-specific mutagenesis without phenotypic selection. Proc Natl Acad Sci U S A. 1985 Jan;82(2):488–492. doi: 10.1073/pnas.82.2.488. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Lee M. S., Enoch T., Piwnica-Worms H. mik1+ encodes a tyrosine kinase that phosphorylates p34cdc2 on tyrosine 15. J Biol Chem. 1994 Dec 2;269(48):30530–30537. [PubMed] [Google Scholar]
  40. Lee M. S., Ogg S., Xu M., Parker L. L., Donoghue D. J., Maller J. L., Piwnica-Worms H. cdc25+ encodes a protein phosphatase that dephosphorylates p34cdc2. Mol Biol Cell. 1992 Jan;3(1):73–84. doi: 10.1091/mbc.3.1.73. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Levedakou E. N., He M., Baptist E. W., Craven R. J., Cance W. G., Welcsh P. L., Simmons A., Naylor S. L., Leach R. J., Lewis T. B. Two novel human serine/threonine kinases with homologies to the cell cycle regulating Xenopus MO15, and NIMA kinases: cloning and characterization of their expression pattern. Oncogene. 1994 Jul;9(7):1977–1988. [PubMed] [Google Scholar]
  42. 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]
  43. Matsushime H., Quelle D. E., Shurtleff S. A., Shibuya M., Sherr C. J., Kato J. Y. D-type cyclin-dependent kinase activity in mammalian cells. Mol Cell Biol. 1994 Mar;14(3):2066–2076. doi: 10.1128/mcb.14.3.2066. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Matsushime H., Roussel M. F., Ashmun R. A., Sherr C. J. Colony-stimulating factor 1 regulates novel cyclins during the G1 phase of the cell cycle. Cell. 1991 May 17;65(4):701–713. doi: 10.1016/0092-8674(91)90101-4. [DOI] [PubMed] [Google Scholar]
  45. McGowan C. H., Russell P. Human Wee1 kinase inhibits cell division by phosphorylating p34cdc2 exclusively on Tyr15. EMBO J. 1993 Jan;12(1):75–85. doi: 10.1002/j.1460-2075.1993.tb05633.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Meurs E., Chong K., Galabru J., Thomas N. S., Kerr I. M., Williams B. R., Hovanessian A. G. Molecular cloning and characterization of the human double-stranded RNA-activated protein kinase induced by interferon. Cell. 1990 Jul 27;62(2):379–390. doi: 10.1016/0092-8674(90)90374-n. [DOI] [PubMed] [Google Scholar]
  47. Millar J. B., McGowan C. H., Lenaers G., Jones R., Russell P. p80cdc25 mitotic inducer is the tyrosine phosphatase that activates p34cdc2 kinase in fission yeast. EMBO J. 1991 Dec;10(13):4301–4309. doi: 10.1002/j.1460-2075.1991.tb05008.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. 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]
  49. 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]
  50. Mueller P. R., Coleman T. R., Dunphy W. G. Cell cycle regulation of a Xenopus Wee1-like kinase. Mol Biol Cell. 1995 Jan;6(1):119–134. doi: 10.1091/mbc.6.1.119. [DOI] [PMC free article] [PubMed] [Google Scholar]
  51. Nigg E. A. Cellular substrates of p34(cdc2) and its companion cyclin-dependent kinases. Trends Cell Biol. 1993 Sep;3(9):296–301. doi: 10.1016/0962-8924(93)90011-o. [DOI] [PubMed] [Google Scholar]
  52. 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]
  53. Nurse P. Genetic control of cell size at cell division in yeast. Nature. 1975 Aug 14;256(5518):547–551. doi: 10.1038/256547a0. [DOI] [PubMed] [Google Scholar]
  54. Nurse P., Thuriaux P. Regulatory genes controlling mitosis in the fission yeast Schizosaccharomyces pombe. Genetics. 1980 Nov;96(3):627–637. doi: 10.1093/genetics/96.3.627. [DOI] [PMC free article] [PubMed] [Google Scholar]
  55. Okayama H., Berg P. A cDNA cloning vector that permits expression of cDNA inserts in mammalian cells. Mol Cell Biol. 1983 Feb;3(2):280–289. doi: 10.1128/mcb.3.2.280. [DOI] [PMC free article] [PubMed] [Google Scholar]
  56. Parker L. L., Atherton-Fessler S., Lee M. S., Ogg S., Falk J. L., Swenson K. I., Piwnica-Worms H. Cyclin promotes the tyrosine phosphorylation of p34cdc2 in a wee1+ dependent manner. EMBO J. 1991 May;10(5):1255–1263. doi: 10.1002/j.1460-2075.1991.tb08067.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  57. Parker L. L., Atherton-Fessler S., Piwnica-Worms H. p107wee1 is a dual-specificity kinase that phosphorylates p34cdc2 on tyrosine 15. Proc Natl Acad Sci U S A. 1992 Apr 1;89(7):2917–2921. doi: 10.1073/pnas.89.7.2917. [DOI] [PMC free article] [PubMed] [Google Scholar]
  58. Parker L. L., Piwnica-Worms H. Inactivation of the p34cdc2-cyclin B complex by the human WEE1 tyrosine kinase. Science. 1992 Sep 25;257(5078):1955–1957. doi: 10.1126/science.1384126. [DOI] [PubMed] [Google Scholar]
  59. Parker L. L., Walter S. A., Young P. G., Piwnica-Worms H. Phosphorylation and inactivation of the mitotic inhibitor Wee1 by the nim1/cdr1 kinase. Nature. 1993 Jun 24;363(6431):736–738. doi: 10.1038/363736a0. [DOI] [PubMed] [Google Scholar]
  60. Pines J., Hunter T. Human cyclin A is adenovirus E1A-associated protein p60 and behaves differently from cyclin B. Nature. 1990 Aug 23;346(6286):760–763. doi: 10.1038/346760a0. [DOI] [PubMed] [Google Scholar]
  61. Pines J., Hunter T. Human cyclins A and B1 are differentially located in the cell and undergo cell cycle-dependent nuclear transport. J Cell Biol. 1991 Oct;115(1):1–17. doi: 10.1083/jcb.115.1.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  62. 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]
  63. Pines J., Hunter T. The differential localization of human cyclins A and B is due to a cytoplasmic retention signal in cyclin B. EMBO J. 1994 Aug 15;13(16):3772–3781. doi: 10.1002/j.1460-2075.1994.tb06688.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  64. Rogers S., Wells R., Rechsteiner M. Amino acid sequences common to rapidly degraded proteins: the PEST hypothesis. Science. 1986 Oct 17;234(4774):364–368. doi: 10.1126/science.2876518. [DOI] [PubMed] [Google Scholar]
  65. 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]
  66. Russell P., Nurse P. The mitotic inducer nim1+ functions in a regulatory network of protein kinase homologs controlling the initiation of mitosis. Cell. 1987 May 22;49(4):569–576. doi: 10.1016/0092-8674(87)90459-4. [DOI] [PubMed] [Google Scholar]
  67. 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]
  68. Sebastian B., Kakizuka A., Hunter T. Cdc25M2 activation of cyclin-dependent kinases by dephosphorylation of threonine-14 and tyrosine-15. Proc Natl Acad Sci U S A. 1993 Apr 15;90(8):3521–3524. doi: 10.1073/pnas.90.8.3521. [DOI] [PMC free article] [PubMed] [Google Scholar]
  69. Smythe C., Newport J. W. Coupling of mitosis to the completion of S phase in Xenopus occurs via modulation of the tyrosine kinase that phosphorylates p34cdc2. Cell. 1992 Feb 21;68(4):787–797. doi: 10.1016/0092-8674(92)90153-4. [DOI] [PubMed] [Google Scholar]
  70. Strausfeld U., Labbé J. C., Fesquet D., Cavadore J. C., Picard A., Sadhu K., Russell P., Dorée M. Dephosphorylation and activation of a p34cdc2/cyclin B complex in vitro by human CDC25 protein. Nature. 1991 May 16;351(6323):242–245. doi: 10.1038/351242a0. [DOI] [PubMed] [Google Scholar]
  71. Tang Z., Coleman T. R., Dunphy W. G. Two distinct mechanisms for negative regulation of the Wee1 protein kinase. EMBO J. 1993 Sep;12(9):3427–3436. doi: 10.1002/j.1460-2075.1993.tb06017.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  72. Thuriaux P., Nurse P., Carter B. Mutants altered in the control co-ordinating cell division with cell growth in the fission yeast Schizosaccharomyces pombe. Mol Gen Genet. 1978 May 3;161(2):215–220. doi: 10.1007/BF00274190. [DOI] [PubMed] [Google Scholar]
  73. Warbrick E., Fantes P. A. The wis1 protein kinase is a dosage-dependent regulator of mitosis in Schizosaccharomyces pombe. EMBO J. 1991 Dec;10(13):4291–4299. doi: 10.1002/j.1460-2075.1991.tb05007.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  74. Wu L., Russell P. Nim1 kinase promotes mitosis by inactivating Wee1 tyrosine kinase. Nature. 1993 Jun 24;363(6431):738–741. doi: 10.1038/363738a0. [DOI] [PubMed] [Google Scholar]
  75. Zheng X. F., Ruderman J. V. Functional analysis of the P box, a domain in cyclin B required for the activation of Cdc25. Cell. 1993 Oct 8;75(1):155–164. [PubMed] [Google Scholar]
  76. Zoller M. J., Nelson N. C., Taylor S. S. Affinity labeling of cAMP-dependent protein kinase with p-fluorosulfonylbenzoyl adenosine. Covalent modification of lysine 71. J Biol Chem. 1981 Nov 10;256(21):10837–10842. [PubMed] [Google Scholar]