PDE4A: Difference between revisions

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<!-- The PBB_Controls template provides controls for Protein Box Bot, please see Template:PBB_Controls for details. -->
{{Infobox_gene}}
{{PBB_Controls
'''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  | url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=5141 | date = 2012-03-04 | accessdate = 2012-04-02 }}</ref>
| update_page = yes
| require_manual_inspection = no
| update_protein_box = yes
| update_summary = yes
| update_citations = yes
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<!-- The GNF_Protein_box is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
== Function ==
{{GNF_Protein_box
| image = PBB_Protein_PDE4A_image.jpg
| image_source = [[Protein_Data_Bank|PDB]] rendering based on 1loi.
| PDB = {{PDB2|1loi}}
| Name = Phosphodiesterase 4A, cAMP-specific (phosphodiesterase E2 dunce homolog, Drosophila)
| HGNCid = 8780
| Symbol = PDE4A
| AltSymbols =; DPDE2; PDE4
| OMIM = 600126
| ECnumber = 
| Homologene = 4520
| MGIid = 99558
| GeneAtlas_image1 = PBB_GE_PDE4A_204735_at_tn.png
| GeneAtlas_image2 = PBB_GE_PDE4A_211447_s_at_tn.png
| GeneAtlas_image3 = PBB_GE_PDE4A_211591_s_at_tn.png
| Function = {{GNF_GO|id=GO:0003824 |text = catalytic activity}} {{GNF_GO|id=GO:0004114 |text = 3',5'-cyclic-nucleotide phosphodiesterase activity}} {{GNF_GO|id=GO:0004115 |text = 3',5'-cyclic-AMP phosphodiesterase activity}} {{GNF_GO|id=GO:0016787 |text = hydrolase activity}}
| Component = {{GNF_GO|id=GO:0005575 |text = cellular_component}} {{GNF_GO|id=GO:0005624 |text = membrane fraction}} {{GNF_GO|id=GO:0005625 |text = soluble fraction}} {{GNF_GO|id=GO:0005626 |text = insoluble fraction}}
| Process = {{GNF_GO|id=GO:0007165 |text = signal transduction}} {{GNF_GO|id=GO:0009187 |text = cyclic nucleotide metabolic process}}
| Orthologs = {{GNF_Ortholog_box
    | Hs_EntrezGene = 5141
    | Hs_Ensembl = ENSG00000065989
    | Hs_RefseqProtein = NP_006193
    | Hs_RefseqmRNA = NM_006202
    | Hs_GenLoc_db = 
    | Hs_GenLoc_chr = 19
    | Hs_GenLoc_start = 10388449
    | Hs_GenLoc_end = 10441306
    | Hs_Uniprot = P27815
    | Mm_EntrezGene = 18577
    | Mm_Ensembl = ENSMUSG00000032177
    | Mm_RefseqmRNA = XM_977087
    | Mm_RefseqProtein = XP_982181
    | Mm_GenLoc_db = 
    | Mm_GenLoc_chr = 9
    | Mm_GenLoc_start = 20916193
    | Mm_GenLoc_end = 20962030
    | Mm_Uniprot = O70285
  }}
}}
'''Phosphodiesterase 4A, cAMP-specific (phosphodiesterase E2 dunce homolog, Drosophila)''', also known as '''PDE4A''', is a human [[gene]].<ref name="entrez">{{cite web | title = Entrez Gene: PDE4A phosphodiesterase 4A, cAMP-specific (phosphodiesterase E2 dunce homolog, Drosophila)| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=5141| accessdate = }}</ref>


<!-- The PBB_Summary template is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
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>
{{PBB_Summary
| section_title =  
| summary_text =  
}}


==References==
== Clinical significance ==
{{reflist|2}}
 
==Further reading==
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 | pmc = 4337886 }}</ref>
{{refbegin | 2}}
* [[rolipram]] (antidepressant and antiinflammatory) and [[cilomilast]] (antiinflammatory) – inhibits PDE4A isoforms 1, 2, 6, and 7
{{PBB_Further_reading
* [[roflumilast]] (antiinflammatory) – inhibits PDE4A isoforms 1, 2, and 6
| citations =
 
*{{cite journal  | author=Houslay MD, Schafer P, Zhang KY |title=Keynote review: phosphodiesterase-4 as a therapeutic target. |journal=Drug Discov. Today |volume=10 |issue= 22 |pages= 1503-19 |year= 2006 |pmid= 16257373 |doi= 10.1016/S1359-6446(05)03622-6 }}
== References ==
*{{cite journal | author=Zhang KY, Ibrahim PN, Gillette S, Bollag G |title=Phosphodiesterase-4 as a potential drug target. |journal=Expert Opin. Ther. Targets |volume=9 |issue= 6 |pages= 1283-305 |year= 2006 |pmid= 16300476 |doi= 10.1517/14728222.9.6.1283 }}
{{reflist|33em}}
*{{cite journal | author=Livi GP, Kmetz P, McHale MM, ''et al.'' |title=Cloning and expression of cDNA for a human low-Km, rolipram-sensitive cyclic AMP phosphodiesterase. |journal=Mol. Cell. Biol. |volume=10 |issue= 6 |pages= 2678-86 |year= 1990 |pmid= 2160582 |doi= }}
{{clear}}
*{{cite journal  | author=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=Biochem. J. |volume=308 ( Pt 2) |issue= |pages= 683-91 |year= 1995 |pmid= 7772058 |doi=  }}
 
*{{cite journal | author=Sullivan M, Egerton M, Shakur Y, ''et al.'' |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=Cell. Signal. |volume=6 |issue= 7 |pages= 793-812 |year= 1995 |pmid= 7888306 |doi= }}
== Further reading ==
*{{cite journal | author=Milatovich A, Bolger G, Michaeli T, Francke U |title=Chromosome localizations of genes for five cAMP-specific phosphodiesterases in man and mouse. |journal=Somat. Cell Mol. Genet. |volume=20 |issue= 2 |pages= 75-86 |year= 1994 |pmid= 8009369 |doi= }}
{{refbegin|33em}}
*{{cite journal | author=Bolger G, Michaeli T, Martins T, ''et al.'' |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=Mol. Cell. Biol. |volume=13 |issue= 10 |pages= 6558-71 |year= 1993 |pmid= 8413254 |doi= }}
* {{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 | author=Huston E, Pooley L, Julien P, ''et al.'' |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=J. Biol. Chem. |volume=271 |issue= 49 |pages= 31334-44 |year= 1997 |pmid= 8940140 |doi= }}
* {{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 | author=Sullivan M, Rena G, Begg F, ''et al.'' |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=Biochem. J. |volume=333 ( Pt 3) |issue= |pages= 693-703 |year= 1998 |pmid= 9677330 |doi= }}
* {{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 | author=McPhee I, Yarwood SJ, Scotland G, ''et al.'' |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=J. Biol. Chem. |volume=274 |issue= 17 |pages= 11796-810 |year= 1999 |pmid= 10206997 |doi= }}
* {{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  | author=Zhou L, Thompson WJ, Potter DE |title=Multiple cyclic nucleotide phosphodiesterases in human trabecular meshwork cells. |journal=Invest. Ophthalmol. Vis. Sci. |volume=40 |issue= 8 |pages= 1745-52 |year= 1999 |pmid= 10393044 |doi=  }}
* {{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 | author=Secchiero P, Zella D, Curreli S, ''et al.'' |title=Pivotal role of cyclic nucleoside phosphodiesterase 4 in Tat-mediated CD4+ T cell hyperactivation and HIV type 1 replication. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=97 |issue= 26 |pages= 14620-5 |year= 2001 |pmid= 11114167 |doi= 10.1073/pnas.011512398 }}
* {{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  | author=Zauli G, Milani D, Mirandola P, ''et al.'' |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 J. |volume=15 |issue= 2 |pages= 483-91 |year= 2001 |pmid= 11156964 |doi= 10.1096/fj.00-0354com }}
* {{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 | author=Rena G, Begg F, Ross A, ''et al.'' |title=Molecular cloning, genomic positioning, promoter identification, and characterization of the novel cyclic amp-specific phosphodiesterase PDE4A10. |journal=Mol. Pharmacol. |volume=59 |issue= 5 |pages= 996-1011 |year= 2001 |pmid= 11306681 |doi= }}
* {{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  | author=Lario PI, Bobechko B, Bateman K, ''et al.'' |title=Purification and characterization of the human PDE4A catalytic domain (PDE4A330-723) expressed in Sf9 cells. |journal=Arch. Biochem. Biophys. |volume=394 |issue= 1 |pages= 54-60 |year= 2001 |pmid= 11566027 |doi= 10.1006/abbi.2001.2513 }}
* {{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 | author=Moon E, Lee R, Near R, ''et al.'' |title=Inhibition of PDE3B augments PDE4 inhibitor-induced apoptosis in a subset of patients with chronic lymphocytic leukemia. |journal=Clin. Cancer Res. |volume=8 |issue= 2 |pages= 589-95 |year= 2002 |pmid= 11839681 |doi= }}
* {{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  | author=Laliberté F, Liu S, Gorseth E, ''et al.'' |title=In vitro PKA phosphorylation-mediated human PDE4A4 activation. |journal=FEBS Lett. |volume=512 |issue= 1-3 |pages= 205-8 |year= 2002 |pmid= 11852080 |doi=  }}
* {{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 | author=Baillie GS, Huston E, Scotland G, ''et al.'' |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=J. Biol. Chem. |volume=277 |issue= 31 |pages= 28298-309 |year= 2002 |pmid= 11994273 |doi= 10.1074/jbc.M108353200 }}
* {{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  | author=Strausberg RL, Feingold EA, Grouse LH, ''et al.'' |title=Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 26 |pages= 16899-903 |year= 2003 |pmid= 12477932 |doi= 10.1073/pnas.242603899 }}
* {{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 | author=Pryzwansky KB, Madden VJ |title=Type 4A cAMP-specific phosphodiesterase is stored in granules of human neutrophils and eosinophils. |journal=Cell Tissue Res. |volume=312 |issue= 3 |pages= 301-11 |year= 2004 |pmid= 12764607 |doi= 10.1007/s00441-003-0728-y }}
* {{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}}
{{refend}}


{{protein-stub}}
{{PDB Gallery|geneid=5141}}
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Latest revision as of 23:39, 22 May 2018

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Identifiers
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External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
Entrez

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Ensembl

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UniProt

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RefSeq (mRNA)

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RefSeq (protein)

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Wikidata
View/Edit Human

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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