Encyclopedia of Signaling Molecules

2018 Edition
| Editors: Sangdun Choi


  • Hisashi Tatebe
  • Kazuhiro ShiozakiEmail author
Reference work entry
DOI: https://doi.org/10.1007/978-3-319-67199-4_249


Historical Background

Protein phosphatase 2C (PP2C) was first defined as magnesium (or manganese)-dependent Ser/Thr-specific dephosphorylation activity in mammalian tissue extract (Cohen 1989). This activity was also found to be resistant to okadaic acid, a potent inhibitor of Ser/Thr phosphatases. Because of its cation dependency, PP2C is sometimes referred as PPM (protein phosphatase, magnesium or manganese dependent). Genes encoding PP2C were subsequently isolated from yeast to humans, revealing a conserved protein phosphatase family with no apparent sequence similarity to the other Ser/Thr phosphatases such as PP1, PP2A, and PP2B. It is also notable that eukaryotic species have more genes encoding for PP2C than those for the other Ser/Thr phosphatase families. For example, the budding yeast Saccharomyces cerevisiae and the fission yeast Schizosaccharomyces pombehave seven and six PP2C or...

This is a preview of subscription content, log in to check access.


  1. Barford D, Das AK, Egloff MP. The structure and mechanism of protein phosphatases: insights into catalysis and regulation. Annu Rev Biophys Biomol Struct. 1998;27:133–64.  https://doi.org/10.1146/annurev.biophys.27.1.133.CrossRefPubMedPubMedCentralGoogle Scholar
  2. Brock AK, Willmann R, Kolb D, Grefen L, Lajunen HM, Bethke G, et al. The Arabidopsis mitogen-activated protein kinase phosphatase PP2C5 affects seed germination, stomatal aperture, and abscisic acid-inducible gene expression. Plant Physiol. 2010;153(3):1098–111.  https://doi.org/10.1104/pp.110.156109.CrossRefPubMedPubMedCentralGoogle Scholar
  3. Cohen P. The structure and regulation of protein phosphatases. Annu Rev Biochem. 1989;58:453–508.  https://doi.org/10.1146/annurev.bi.58.070189.002321.CrossRefPubMedGoogle Scholar
  4. Cutler SR, Rodriguez PL, Finkelstein RR, Abrams SR. Abscisic acid: emergence of a core signaling network. Annu Rev Plant Biol. 2010;61:651–79.  https://doi.org/10.1146/annurev-arplant-042809-112122.CrossRefPubMedGoogle Scholar
  5. Fuchs S, Grill E, Meskiene I, Schweighofer A. Type 2C protein phosphatases in plants. FEBS J. 2013;280(2):681–93.  https://doi.org/10.1111/j.1742-4658.2012.08670.x.CrossRefPubMedGoogle Scholar
  6. Goloudina AR, Kochetkova EY, Pospelova TV, Demidov ON. Wip1 phosphatase: between p53 and MAPK kinases pathways. Oncotarget. 2016;7(21):31563–71.  https://doi.org/10.18632/oncotarget.7325.CrossRefPubMedPubMedCentralGoogle Scholar
  7. Hecker M, Pané-Farré J, Völker U. SigB-dependent general stress response in Bacillus subtilis and related gram-positive bacteria. Annu Rev Microbiol. 2007;61:215–36.  https://doi.org/10.1146/annurev.micro.61.080706.093445.CrossRefPubMedGoogle Scholar
  8. Hilbert DW, Piggot PJ. Compartmentalization of gene expression during Bacillus subtilis spore formation. Microbiol Mol Biol Rev. 2004;68(2):234–62.  https://doi.org/10.1128/MMBR.68.2.234-262.2004.CrossRefPubMedPubMedCentralGoogle Scholar
  9. Hohmann S. Osmotic stress signaling and osmoadaptation in yeasts. Microbiol Mol Biol Rev. 2002;66(2):300.  https://doi.org/10.1128/MMBR.66.2.300-372.2002.CrossRefPubMedPubMedCentralGoogle Scholar
  10. Hubbard KE, Nishimura N, Hitomi K, Getzoff ED, Schroeder JI. Early abscisic acid signal transduction mechanisms: newly discovered components and newly emerging questions. Genes Dev. 2010;24(16):1695–708.  https://doi.org/10.1101/gad.1953910.CrossRefPubMedPubMedCentralGoogle Scholar
  11. Lammers T, Lavi S. Role of type 2C protein phosphatases in growth regulation and in cellular stress signaling. Crit Rev Biochem Mol Biol. 2007;42(6):437–61.  https://doi.org/10.1080/10409230701693342.CrossRefPubMedGoogle Scholar
  12. Lu X, Nguyen TA, Moon SH, Darlington Y, Sommer M, Donehower LA. The type 2C phosphatase wip1: an oncogenic regulator of tumor suppressor and DNA damage response pathways. Cancer Metastasis Rev. 2008;27(2):123–35.  https://doi.org/10.1007/s10555-008-9127-x.CrossRefPubMedPubMedCentralGoogle Scholar
  13. Lu G, Wang Y. Functional diversity of mammalian type 2C protein phosphatase isoforms: new tales from an old family. Clin Exp Pharmacol Physiol. 2008;35(2):107–12.  https://doi.org/10.1111/j.1440-1681.2007.04843.x.CrossRefPubMedGoogle Scholar
  14. Martín H, Flández M, Nombela C, Molina M. Protein phosphatases in MAPK signalling: we keep learning from yeast. Mol Microbiol. 2005;58(1):6–16.  https://doi.org/10.1111/j.1365-2958.2005.04822.x.CrossRefPubMedGoogle Scholar
  15. Miyakawa T, Fujita Y, Yamaguchi-Shinozaki K, Tanokura M. Structure and function of abscisic acid receptors. Trends Plant Sci. 2013;18(5):259–66.  https://doi.org/10.1016/j.tplants.2012.11.002.CrossRefPubMedGoogle Scholar
  16. Ng LM, Melcher K, Teh BT, Xu HE. Abscisic acid perception and signaling: structural mechanisms and applications. Acta Pharmacol Sin. 2014;35(5):567–84.  https://doi.org/10.1038/aps.2014.5.CrossRefPubMedPubMedCentralGoogle Scholar
  17. Schweighofer A, Kazanaviciute V, Scheikl E, Teige M, Doczi R, Hirt H, et al. The PP2C-type phosphatase AP2C1, which negatively regulates MPK4 and MPK6, modulates innate immunity, jasmonic acid, and ethylene levels in Arabidopsis. Plant Cell. 2007;19(7):2213–24.  https://doi.org/10.1105/tpc.106.049585.CrossRefPubMedPubMedCentralGoogle Scholar
  18. Shi Y. Serine/threonine phosphatases: mechanism through structure. Cell. 2009;139(3):468–84.  https://doi.org/10.1016/j.cell.2009.10.006.CrossRefPubMedCentralPubMedGoogle Scholar
  19. Xue T, Wang D, Zhang S, Ehlting J, Ni F, Jakab S, et al. Genome-wide and expression analysis of protein phosphatase 2C in rice and Arabidopsis. BMC Genomics. 2008;9:550.  https://doi.org/10.1186/1471-2164-9-550.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  1. 1.Graduate School of Biological SciencesNara Institute of Science and TechnologyNaraJapan
  2. 2.Department of Microbiology and Molecular GeneticsUniversity of California, DavisDavisUSA