PDE4A

2017-10-04T22:13:56Z

24.24.156.195: /* Function */

{{Infobox_gene}}
'''cAMP-specific 3',5'-cyclic phosphodiesterase 4A''' is an [[enzyme]] that in humans is encoded by the ''PDE4A'' [[gene]].<ref name="pmid8009369">{{cite journal | vauthors = Milatovich A, Bolger G, Michaeli T, Francke U | title = Chromosome localizations of genes for five cAMP-specific phosphodiesterases in man and mouse | journal = Somatic Cell and Molecular Genetics | volume = 20 | issue = 2 | pages = 75–86 | date = Mar 1994 | pmid = 8009369 | pmc = | doi = 10.1007/BF02290677 }}</ref><ref name="entrez">{{cite web | title = PDE4A phosphodiesterase 4A, cAMP-specific ( ''Homo sapiens'' ) | work = Entrez Gene | publisher = NCBI | url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=5141 | date = 2012-03-04 | accessdate = 2012-04-02 }}</ref>

== Function ==

The protein encoded by this gene belongs to the [[cyclic nucleotide phosphodiesterase]] (PDE) family, and [[PDE4]] subfamily. This PDE [[hydrolyzes]] the secondary messenger, [[cyclic adenosine monophosphate|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.<ref name="entrez"/> 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.<ref>{{cite journal | vauthors = Hansen RT, Conti M, ((Zhang H-T)) | year = 2014 | title = Mice deficient in phosphodiesterase-4A display anxiogenic-like behavior | url = | journal = Psychopharmacology | volume = 231| issue = | pages = 2941–2954| doi = 10.1007/s00213-014-3480-y | pmid=24563185}}</ref>

== Clinical significance ==

PDE4A is a target of a number of drugs including:<ref name="pmid11306681">{{cite journal | vauthors = Rena G, Begg F, Ross A, MacKenzie C, McPhee I, Campbell L, Huston E, Sullivan M, Houslay MD | title = Molecular cloning, genomic positioning, promoter identification, and characterization of the novel cyclic amp-specific phosphodiesterase PDE4A10 | journal = Molecular Pharmacology | volume = 59 | issue = 5 | pages = 996–1011 | date = May 2001 | pmid = 11306681 | url = http://molpharm.aspetjournals.org/content/59/5/996.full.pdf | format = pdf }}</ref><ref name="pmid15738310">{{cite journal | vauthors = 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 | title = Identification and characterization of PDE4A11, a novel, widely expressed long isoform encoded by the human PDE4A cAMP phosphodiesterase gene | journal = Molecular Pharmacology | volume = 67 | issue = 6 | pages = 1920–34 | date = Jun 2005 | pmid = 15738310 | doi = 10.1124/mol.104.009423 }}</ref><ref name="pmid18095939">{{cite journal | vauthors = 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 | title = Human PDE4A8, a novel brain-expressed PDE4 cAMP-specific phosphodiesterase that has undergone rapid evolutionary change | journal = The Biochemical Journal | volume = 411 | issue = 2 | pages = 361–9 | date = Apr 2008 | pmid = 18095939 | doi = 10.1042/BJ20071251 }}</ref>
* [[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 ==
{{reflist|33em}}
{{clear}}

== Further reading ==
{{refbegin|33em}}
* {{cite journal | vauthors = Houslay MD, Schafer P, Zhang KY | title = Keynote review: phosphodiesterase-4 as a therapeutic target | journal = Drug Discovery Today | volume = 10 | issue = 22 | pages = 1503–19 | date = Nov 2005 | pmid = 16257373 | doi = 10.1016/S1359-6446(05)03622-6 }}
* {{cite journal | vauthors = Zhang KY, Ibrahim PN, Gillette S, Bollag G | title = Phosphodiesterase-4 as a potential drug target | journal = Expert Opinion on Therapeutic Targets | volume = 9 | issue = 6 | pages = 1283–305 | date = Dec 2005 | pmid = 16300476 | doi = 10.1517/14728222.9.6.1283 }}
* {{cite journal | vauthors = Livi GP, Kmetz P, McHale MM, Cieslinski LB, Sathe GM, Taylor DP, Davis RL, Torphy TJ, Balcarek JM | title = Cloning and expression of cDNA for a human low-Km, rolipram-sensitive cyclic AMP phosphodiesterase | journal = Molecular and Cellular Biology | volume = 10 | issue = 6 | pages = 2678–86 | date = Jun 1990 | pmid = 2160582 | pmc = 360627 | doi = 10.1128/MCB.10.6.2678 | url = https://www.ncbi.nlm.nih.gov/pmc/articles/PMC360627/pdf/molcellb00042-0248.pdf | format = pdf }}
* {{cite journal | vauthors = Horton YM, Sullivan M, Houslay MD | title = Molecular cloning of a novel splice variant of human type IVA (PDE-IVA) cyclic AMP phosphodiesterase and localization of the gene to the p13.2-q12 region of human chromosome 19 [corrected] | journal = The Biochemical Journal | volume = 308 | issue = 2 | pages = 683–91 | date = Jun 1995 | pmid = 7772058 | pmc = 1136980 | url = http://www.biochemj.org/bj/308/0683/3080683.pdf | format = pdf | doi=10.1042/bj3080683}}
* {{cite journal | vauthors = Sullivan M, Egerton M, Shakur Y, Marquardsen A, Houslay MD | title = 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) | journal = Cellular Signalling | volume = 6 | issue = 7 | pages = 793–812 | date = Sep 1994 | pmid = 7888306 | doi = 10.1016/0898-6568(94)00039-5 }}
* {{cite journal | vauthors = Bolger G, Michaeli T, Martins T, St John T, Steiner B, Rodgers L, Riggs M, Wigler M, Ferguson K | title = A family of human phosphodiesterases homologous to the dunce learning and memory gene product of Drosophila melanogaster are potential targets for antidepressant drugs | journal = Molecular and Cellular Biology | volume = 13 | issue = 10 | pages = 6558–71 | date = Oct 1993 | pmid = 8413254 | pmc = 364715 | url = https://www.ncbi.nlm.nih.gov/pmc/articles/PMC364715/pdf/molcellb00022-0642.pdf | format = pdf | doi=10.1128/mcb.13.10.6558}}
* {{cite journal | vauthors = Huston E, Pooley L, Julien P, Scotland G, McPhee I, Sullivan M, Bolger G, Houslay MD | title = The human cyclic AMP-specific phosphodiesterase PDE-46 (HSPDE4A4B) expressed in transfected COS7 cells occurs as both particulate and cytosolic species that exhibit distinct kinetics of inhibition by the antidepressant rolipram | journal = The Journal of Biological Chemistry | volume = 271 | issue = 49 | pages = 31334–44 | date = Dec 1996 | pmid = 8940140 | doi = 10.1074/jbc.271.49.31334 | url = http://www.jbc.org/content/271/49/31334.full.pdf | format = pdf }}
* {{cite journal | vauthors = Sullivan M, Rena G, Begg F, Gordon L, Olsen AS, Houslay MD | title = Identification and characterization of the human homologue of the short PDE4A cAMP-specific phosphodiesterase RD1 (PDE4A1) by analysis of the human HSPDE4A gene locus located at chromosome 19p13.2 | journal = The Biochemical Journal | volume = 333 | issue = 3 | pages = 693–703 | date = Aug 1998 | pmid = 9677330 | pmc = 1219634 | url = https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1219634/pdf/9677330.pdf | format = pdf | doi=10.1042/bj3330693}}
* {{cite journal | vauthors = McPhee I, Yarwood SJ, Scotland G, Huston E, Beard MB, Ross AH, Houslay ES, Houslay MD | title = Association with the SRC family tyrosyl kinase LYN triggers a conformational change in the catalytic region of human cAMP-specific phosphodiesterase HSPDE4A4B. Consequences for rolipram inhibition | journal = The Journal of Biological Chemistry | volume = 274 | issue = 17 | pages = 11796–810 | date = Apr 1999 | pmid = 10206997 | doi = 10.1074/jbc.274.17.11796 | url = http://www.jbc.org/content/274/17/11796.full.pdf | format = pdf }}
* {{cite journal | vauthors = Zhou L, Thompson WJ, Potter DE | title = Multiple cyclic nucleotide phosphodiesterases in human trabecular meshwork cells | journal = Investigative Ophthalmology & Visual Science | volume = 40 | issue = 8 | pages = 1745–52 | date = Jul 1999 | pmid = 10393044 | url = http://www.iovs.org/content/40/8/1745.full.pdf | format = pdf }}
* {{cite journal | vauthors = Secchiero P, Zella D, Curreli S, Mirandola P, Capitani S, Gallo RC, Zauli G | title = Pivotal role of cyclic nucleoside phosphodiesterase 4 in Tat-mediated CD4+ T cell hyperactivation and HIV type 1 replication | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 97 | issue = 26 | pages = 14620–5 | date = Dec 2000 | pmid = 11114167 | pmc = 18968 | doi = 10.1073/pnas.011512398 | url = https://www.ncbi.nlm.nih.gov/pmc/articles/PMC18968/pdf/pq014620.pdf | format = pdf }}
* {{cite journal | vauthors = Zauli G, Milani D, Mirandola P, Mazzoni M, Secchiero P, Miscia S, Capitani S | title = HIV-1 Tat protein down-regulates CREB transcription factor expression in PC12 neuronal cells through a phosphatidylinositol 3-kinase/AKT/cyclic nucleoside phosphodiesterase pathway | journal = FASEB Journal | volume = 15 | issue = 2 | pages = 483–91 | date = Feb 2001 | pmid = 11156964 | doi = 10.1096/fj.00-0354com | url = http://www.fasebj.org/content/15/2/483.full.pdf | format = pdf }}
* {{cite journal | vauthors = Lario PI, Bobechko B, Bateman K, Kelly J, Vrielink A, Huang Z | title = Purification and characterization of the human PDE4A catalytic domain (PDE4A330-723) expressed in Sf9 cells | journal = Archives of Biochemistry and Biophysics | volume = 394 | issue = 1 | pages = 54–60 | date = Oct 2001 | pmid = 11566027 | doi = 10.1006/abbi.2001.2513 }}
* {{cite journal | vauthors = Moon E, Lee R, Near R, Weintraub L, Wolda S, Lerner A | title = Inhibition of PDE3B augments PDE4 inhibitor-induced apoptosis in a subset of patients with chronic lymphocytic leukemia | journal = Clinical Cancer Research | volume = 8 | issue = 2 | pages = 589–95 | date = Feb 2002 | pmid = 11839681 | url = http://clincancerres.aacrjournals.org/content/8/2/589.full.pdf | format = pdf }}
* {{cite journal | vauthors = Laliberté F, Liu S, Gorseth E, Bobechko B, Bartlett A, Lario P, Gresser MJ, Huang Z | title = In vitro PKA phosphorylation-mediated human PDE4A4 activation | journal = FEBS Letters | volume = 512 | issue = 1–3 | pages = 205–8 | date = Feb 2002 | pmid = 11852080 | doi = 10.1016/S0014-5793(02)02259-7 | url = http://www.sciencedirect.com/science/article/pii/S0014579302022597 }}
* {{cite journal | vauthors = Baillie GS, Huston E, Scotland G, Hodgkin M, Gall I, Peden AH, MacKenzie C, Houslay ES, Currie R, Pettitt TR, Walmsley AR, Wakelam MJ, Warwicker J, Houslay MD | title = TAPAS-1, a novel microdomain within the unique N-terminal region of the PDE4A1 cAMP-specific phosphodiesterase that allows rapid, Ca2+-triggered membrane association with selectivity for interaction with phosphatidic acid | journal = The Journal of Biological Chemistry | volume = 277 | issue = 31 | pages = 28298–309 | date = Aug 2002 | pmid = 11994273 | doi = 10.1074/jbc.M108353200 | url = http://www.jbc.org/content/277/31/28298.full.pdf | format = pdf }}
* {{cite journal | vauthors = Pryzwansky KB, Madden VJ | title = Type 4A cAMP-specific phosphodiesterase is stored in granules of human neutrophils and eosinophils | journal = Cell and Tissue Research | volume = 312 | issue = 3 | pages = 301–11 | date = Jun 2003 | pmid = 12764607 | doi = 10.1007/s00441-003-0728-y }}
{{refend}}

{{PDB Gallery|geneid=5141}}
{{Esterases}}

{{NLM content}}

wikidoc - User contributions [en]

PDE4A