Encyclopedia of Signaling Molecules

2018 Edition
| Editors: Sangdun Choi

WEE1

  • Nobumoto Watanabe
Reference work entry
DOI: https://doi.org/10.1007/978-3-319-67199-4_101526

Synonyms

 WEE1A;  WEE1Hu

Historical Background

Originally, WEE1 was isolated as a gene responsible for the “wee” phenotype in fission yeast (Russell and Nurse 1987). WEE1 from fission yeast has been shown to autophosphorylate at serine and tyrosine residues, although the exact role of serine phosphorylation is still unknown. WEE1 from fission yeast and other species has been shown to phosphorylate cyclin-associated CDK at Tyr 15; this residue is located near the ATP-binding pocket of CDK. Another WEE1 family member, Myt1, can phosphorylate Thr 14 and Tyr 15 of CDKs. However, Myt1 preferentially phosphorylates Thr 14; thus, WEE1 is considered to be principally responsible for Tyr 15 phosphorylation.

WEE1 is a protein kinase, and the catalytic domain has been categorized as a serine/threonine kinase rather than a tyrosine kinase (Fig. 1). However, WEE1 has been observed to phosphorylate serine, threonine, and tyrosine residues of its substrates, making it a dual-specificity protein...
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References

  1. Honda R, Ohba Y, Yasuda H. 14-3-3 zeta protein binds to the carboxyl half of mouse wee1 kinase. Biochem Biophys Res Commun. 1997;230:262–5. doi:10.1006/bbrc.1996.5933.CrossRefPubMedPubMedCentralGoogle Scholar
  2. Honda R, Tanaka H, Ohba Y, Yasuda H. Mouse p87wee1 kinase is regulated by M-phase specific phosphorylation. Chromosom Res. 1995;3:300–8.CrossRefGoogle Scholar
  3. Igarashi M, Nagata A, Jinno S, Suto K, Okayama H. Wee1(+)-like gene in human cells. Nature. 1991;353:80–3. doi:10.1038/353080a0.CrossRefPubMedPubMedCentralGoogle Scholar
  4. Katayama K, Fujita N, Tsuruo T. Akt/protein kinase B-dependent phosphorylation and inactivation of WEE1Hu promote cell cycle progression at G2/M transition. Mol Cell Biol. 2005;25:5725–37. doi:10.1128/MCB.25.13.5725-5737.2005.CrossRefPubMedPubMedCentralGoogle Scholar
  5. Lee J, Kumagai A, Dunphy WG. Positive regulation of Wee1 by Chk1 and 14-3-3 proteins. Mol Biol Cell. 2001;12:551–63.PubMedPubMedCentralCrossRefGoogle Scholar
  6. Leise 3rd W, Mueller PR. Multiple Cdk1 inhibitory kinases regulate the cell cycle during development. Dev Biol. 2002;249:156–73.PubMedPubMedCentralCrossRefGoogle Scholar
  7. Matsuo T, Yamaguchi S, Mitsui S, Emi A, Shimoda F, Okamura H. Control mechanism of the circadian clock for timing of cell division in vivo. Science. 2003;302:255–9. doi:10.1126/science.1086271.CrossRefPubMedPubMedCentralGoogle Scholar
  8. McGowan CH, Russell P. Human Wee1 kinase inhibits cell division by phosphorylating p34cdc2 exclusively on Tyr15. EMBO J. 1993;12:75–85.PubMedPubMedCentralCrossRefGoogle Scholar
  9. Nakanishi M, Ando H, Watanabe N, Kitamura K, Ito K, Okayama H, et al. Identification and characterization of human Wee1B, a new member of the Wee1 family of Cdk-inhibitory kinases. Genes Cells. 2000;5:839–47.PubMedPubMedCentralCrossRefGoogle Scholar
  10. Okamoto K, Sagata N. Mechanism for inactivation of the mitotic inhibitory kinase Wee1 at M phase. Proc Natl Acad Sci USA. 2007;104:3753–8. doi:10.1073/pnas.0607357104.CrossRefPubMedPubMedCentralGoogle Scholar
  11. Price DM, Jin Z, Rabinovitch S, Campbell SD. Ectopic expression of the Drosophila Cdk1 inhibitory kinases, Wee1 and Myt1, interferes with the second mitotic wave and disrupts pattern formation during eye development. Genetics. 2002;161:721–31.PubMedPubMedCentralGoogle Scholar
  12. Rothblum-Oviatt CJ, Ryan CE, Piwnica-Worms H. 14-3-3 binding regulates catalytic activity of human Wee1 kinase. Cell Growth Differ. 2001;12:581–9.PubMedGoogle Scholar
  13. Russell P, Nurse P. Negative regulation of mitosis by wee1+, a gene encoding a protein kinase homolog. Cell. 1987;49:559–67.PubMedCrossRefGoogle Scholar
  14. Tominaga Y, Li C, Wang RH, Deng CX. Murine Wee1 plays a critical role in cell cycle regulation and pre-implantation stages of embryonic development. Int J Biol Sci. 2006;2:161–70.PubMedPubMedCentralCrossRefGoogle Scholar
  15. Wang Y, Jacobs C, Hook KE, Duan H, Booher RN, Sun Y. Binding of 14-3-3beta to the carboxyl terminus of Wee1 increases Wee1 stability, kinase activity, and G2-M cell population. Cell Growth Differ. 2000;11:211–9.PubMedGoogle Scholar
  16. Wang Y, Li J, Booher RN, Kraker A, Lawrence T, Leopold WR, et al. Radiosensitization of p53 mutant cells by PD0166285, a novel G(2) checkpoint abrogator. Cancer Res. 2001;61:8211–7.PubMedGoogle Scholar
  17. Watanabe N, Broome M, Hunter T. Regulation of the human WEE1Hu CDK tyrosine 15-kinase during the cell cycle. EMBO J. 1995;14:1878–91.PubMedPubMedCentralCrossRefGoogle Scholar
  18. Watanabe N, Arai H, Nishihara Y, Taniguchi M, Watanabe N, Hunter T, et al. M-phase kinases induce phospho-dependent ubiquitination of somatic Wee1 by SCFbeta-TrCP. Proc Natl Acad Sci USA. 2004;101:4419–24. doi:10.1073/pnas.0307700101.CrossRefPubMedPubMedCentralGoogle Scholar
  19. Watanabe N, Arai H, Iwasaki J, Shiina M, Ogata K, Hunter T, et al. Cyclin-dependent kinase (CDK) phosphorylation destabilizes somatic Wee1 via multiple pathways. Proc Natl Acad Sci USA. 2005;102:11663–8. doi:10.1073/pnas.0500410102.CrossRefPubMedPubMedCentralGoogle Scholar
  20. Yu Y, Chen B, Chen Z, Fan C, Han Y, Zhang J, et al. Identification of a novel Wee1 isoform. Biochim Biophys Acta. 2005;1729:1–9. doi:10.1016/j.bbaexp.2005.02.006.CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  1. 1.Bio-Active Compounds Discovery Research UnitRIKEN Center for Sustainable Resource ScienceWakoJapan