Skip to main content

PDE2A

  • Living reference work entry
  • First Online:
  • 96 Accesses

Synonyms

CGS-PDE; Cyclic GMP-stimulated phosphodiesterase; Phosphodiesterase 2A

Historical Background

Half a decade ago, the cyclic nucleotides cyclic adenosine 3′, 5′-monophosphate (cAMP) and cyclic guanosine 3′, 5′-monophosphate (cGMP) were identified as key second messenger molecules that mediate the intracellular effects of many signals known as “first messengers,” such as hormones or neurotransmitters. cAMP and cGMP signaling pathways regulate a vast number of physiological processes, including cell proliferation and differentiation, gene expression, apoptosis, and several metabolic processes, such as insulin secretion, glycogen synthesis, or lipogenesis. After their discovery, many years elapsed before cyclic nucleotides signaling proved to be a selective and effective process to modulate biological pathways. Since then, it has become clear that signaling by cyclic nucleotides modulates a countless number of biological functions, thus requiring a thigh control of their...

This is a preview of subscription content, log in via an institution.

References

  • Acin-Perez R, Russwurm M, Günnewig K, Gertz M, Zoidl G, Ramos L, et al. A phosphodiesterase 2A isoform localized to mitochondria regulates respiration. J Biol Chem. 2011;286(35):30423–32.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Aye T-T, Soni S, van Veen TAB, van der Heyden MAG, Cappadona S, Varro A, et al. Reorganized PKA-AKAP associations in the failing human heart. J Mol Cell Cardiol. 2012;52(2):511–8.

    Article  CAS  PubMed  Google Scholar 

  • Azevedo MF, Faucz FR, Bimpaki E, Horvath A, Levy I, de Alexandre RB, et al. Clinical and molecular genetics of the phosphodiesterases (PDEs). Endocr Rev. 2014;35(2):195–233.

    Article  CAS  PubMed  Google Scholar 

  • Boess FG, Hendrix M, van der Staay F-J, Erb C, Schreiber R, van Staveren W, et al. Inhibition of phosphodiesterase 2 increases neuronal cGMP, synaptic plasticity and memory performance. Neuropharmacology. 2004;47(7):1081–92.

    Article  CAS  PubMed  Google Scholar 

  • Francis SH, Corbin JD, Bischoff E. Cyclic GMP-hydrolyzing phosphodiesterases. Handb Exp Pharmacol. 2009;191:367–408.

    Article  CAS  Google Scholar 

  • Gasser C, Taiber S, Yeh C-M, Wittig CH, Hegemann P, Ryu S, et al. Engineering of a red-light-activated human cAMP/cGMP-specific phosphodiesterase. Proc Natl Acad Sci U S A. 2014;111(24):8803–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gomez L, Breitenbucher JG. PDE2 inhibition: potential for the treatment of cognitive disorders. Bioorg Med Chem Lett. 2013;23(24):6522–7.

    Article  CAS  PubMed  Google Scholar 

  • Martins TJ, Mumby MC, Beavo JA. Purification and characterization of a cyclic GMP-stimulated cyclic nucleotide phosphodiesterase from bovine tissues. J Biol Chem. 1982;257(4):1973–9.

    CAS  PubMed  Google Scholar 

  • Maurice DH, Ke H, Ahmad F, Wang Y, Chung J, Manganiello VC. Advances in targeting cyclic nucleotide phosphodiesterases. Nat Rev Drug Discov. 2014;13(4):290–314.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Morita H, Murata T, Shimizu K, Okumura K, Inui M, Tagawa T. Characterization of phosphodiesterase 2A in human malignant melanoma PMP cells. Oncol Rep. 2013;29(4):1275–84.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Pandit J, Forman MD, Fennell KF, Dillman KS, Menniti FS. Mechanism for the allosteric regulation of phosphodiesterase 2A deduced from the X-ray structure of a near full-length construct. Proc Natl Acad Sci USA. 2009;106(43):18225–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Russwurm C, Zoidl G, Koesling D, Russwurm M. Dual acylation of PDE2A splice variant 3: targeting to synaptic membranes. J Biol Chem. 2009;284(38):25782–90.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Stephenson DT, Coskran TM, Wilhelms MB, Adamowicz WO, O’Donnell MM, Muravnick KB, et al. Immunohistochemical localization of phosphodiesterase 2A in multiple mammalian species. J Histochem Cytochem Off J Histochem Soc. 2009;57(10):933–49.

    Article  CAS  Google Scholar 

  • Vettel C, Lämmle S, Ewens S, Cervirgen C, Emons J, Ongherth A, et al. PDE2-mediated cAMP hydrolysis accelerates cardiac fibroblast to myofibroblast conversion and is antagonized by exogenous activation of cGMP signaling pathways. Am J Physiol Heart Circ Physiol. 2014;306(8):H1246–52.

    Article  CAS  PubMed  Google Scholar 

  • Zaccolo M, Movsesian MA. cAMP and cGMP signaling cross-talk: role of phosphodiesterases and implications for cardiac pathophysiology. Circ Res. 2007;100(11):1569–78.

    Article  CAS  PubMed  Google Scholar 

  • Zhang KYJ, Card GL, Suzuki Y, Artis DR, Fong D, Gillette S, et al. A glutamine switch mechanism for nucleotide selectivity by phosphodiesterases. Mol Cell. 2004;15(2):279–86.

    Article  CAS  PubMed  Google Scholar 

  • Zhu J, Yang Q, Dai D, Huang Q. X-ray crystal structure of phosphodiesterase 2 in complex with a highly selective, nanomolar inhibitor reveals a binding-induced pocket important for selectivity. J Am Chem Soc. 2013;135(32):11708–11.

    Article  CAS  PubMed  Google Scholar 

  • Zoccarato A, Surdo NC, Aronsen JM, Fields LA, Mancuso L, Dodoni G, et al. Cardiac hypertrophy is inhibited by a local pool of cAMP regulated by phosphodiesterase 2. Circ Res. 2015;117(8):707–19.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Miguel J. Lobo .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2016 Springer Science+Business Media LLC

About this entry

Cite this entry

Lobo, M.J., Zaccolo, M. (2016). PDE2A. In: Choi, S. (eds) Encyclopedia of Signaling Molecules. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-6438-9_101603-1

Download citation

  • DOI: https://doi.org/10.1007/978-1-4614-6438-9_101603-1

  • Received:

  • Accepted:

  • Published:

  • Publisher Name: Springer, New York, NY

  • Online ISBN: 978-1-4614-6438-9

  • eBook Packages: Springer Reference Biomedicine and Life SciencesReference Module Biomedical and Life Sciences

Publish with us

Policies and ethics