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. 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.
PDE4A is a target of a number of drugs including:
rolipram (antidepressant and antiinflammatory) and cilomilast (antiinflammatory) – inhibits PDE4A isoforms 1, 2, 6, and 7
roflumilast (antiinflammatory) – inhibits PDE4A isoforms 1, 2, and 6
↑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. PMID8009369.
↑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. PMID15738310.
Zhang KY, Ibrahim PN, Gillette S, Bollag G (Dec 2005). "Phosphodiesterase-4 as a potential drug target". Expert Opinion on Therapeutic Targets. 9 (6): 1283–305. doi:10.1517/14728188.8.131.523. PMID16300476.
Sullivan M, Egerton M, Shakur Y, Marquardsen A, Houslay MD (Sep 1994). "Molecular cloning and expression, in both COS-1 cells and S. cerevisiae, of a human cytosolic type-IVA, cyclic AMP specific phosphodiesterase (hPDE-IVA-h6.1)". Cellular Signalling. 6 (7): 793–812. doi:10.1016/0898-6568(94)00039-5. PMID7888306.
Lario PI, Bobechko B, Bateman K, Kelly J, Vrielink A, Huang Z (Oct 2001). "Purification and characterization of the human PDE4A catalytic domain (PDE4A330-723) expressed in Sf9 cells". Archives of Biochemistry and Biophysics. 394 (1): 54–60. doi:10.1006/abbi.2001.2513. PMID11566027.
Pryzwansky KB, Madden VJ (Jun 2003). "Type 4A cAMP-specific phosphodiesterase is stored in granules of human neutrophils and eosinophils". Cell and Tissue Research. 312 (3): 301–11. doi:10.1007/s00441-003-0728-y. PMID12764607.