PDE4A

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SpeciesHumanMouse
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RefSeq (protein)

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cAMP-specific 3',5'-cyclic phosphodiesterase 4A is an enzyme that in humans is encoded by the PDE4A gene.[1][2]

Function

The protein encoded by this gene belongs to the cyclic nucleotide phosphodiesterase (PDE) family, and PDE4 subfamily. This PDE hydrolyzes the secondary messenger, cAMP, which is a regulator and mediator of a number of cellular responses to extracellular signals. Thus, by regulating the cellular concentration of cAMP, this protein plays a key role in many important physiological processes.[2] Recently, it has been shown through the use of PDE4A knock out mice that PDE4A may play a role in the regulation of anxiety and emotional memory.[3]

Clinical significance

PDE4A is a target of a number of drugs including:[4][5][6]

  • rolipram (antidepressant and antiinflammatory) and cilomilast (antiinflammatory) – inhibits PDE4A isoforms 1, 2, 6, and 7
  • roflumilast (antiinflammatory) – inhibits PDE4A isoforms 1, 2, and 6

References

  1. Milatovich A, Bolger G, Michaeli T, Francke U (Mar 1994). "Chromosome localizations of genes for five cAMP-specific phosphodiesterases in man and mouse". Somatic Cell and Molecular Genetics. 20 (2): 75–86. doi:10.1007/BF02290677. PMID 8009369.
  2. 2.0 2.1 "PDE4A phosphodiesterase 4A, cAMP-specific ( Homo sapiens )". Entrez Gene. 2012-03-04. Retrieved 2012-04-02.
  3. Hansen RT, Conti M, Zhang H-T (2014). "Mice deficient in phosphodiesterase-4A display anxiogenic-like behavior". Psychopharmacology. 231: 2941–2954. doi:10.1007/s00213-014-3480-y. PMID 24563185.
  4. Rena G, Begg F, Ross A, MacKenzie C, McPhee I, Campbell L, Huston E, Sullivan M, Houslay MD (May 2001). "Molecular cloning, genomic positioning, promoter identification, and characterization of the novel cyclic amp-specific phosphodiesterase PDE4A10" (pdf). Molecular Pharmacology. 59 (5): 996–1011. PMID 11306681.
  5. Wallace DA, Johnston LA, Huston E, MacMaster D, Houslay TM, Cheung YF, Campbell L, Millen JE, Smith RA, Gall I, Knowles RG, Sullivan M, Houslay MD (Jun 2005). "Identification and characterization of PDE4A11, a novel, widely expressed long isoform encoded by the human PDE4A cAMP phosphodiesterase gene". Molecular Pharmacology. 67 (6): 1920–34. doi:10.1124/mol.104.009423. PMID 15738310.
  6. Mackenzie KF, Topping EC, Bugaj-Gaweda B, Deng C, Cheung YF, Olsen AE, Stockard CR, High Mitchell L, Baillie GS, Grizzle WE, De Vivo M, Houslay MD, Wang D, Bolger GB (Apr 2008). "Human PDE4A8, a novel brain-expressed PDE4 cAMP-specific phosphodiesterase that has undergone rapid evolutionary change". The Biochemical Journal. 411 (2): 361–9. doi:10.1042/BJ20071251. PMC 4337886. PMID 18095939.

Further reading

This article incorporates text from the United States National Library of Medicine, which is in the public domain.


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