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{{Infobox_gene}}
{{PBB_Controls
'''cAMP-specific 3',5'-cyclic phosphodiesterase 4B''' is an [[enzyme]] that in humans is encoded by the ''PDE4B'' [[gene]].<ref name="entrez">{{cite web | title = Entrez Gene: PDE4B phosphodiesterase 4B, cAMP-specific (phosphodiesterase E4 dunce homolog, Drosophila)| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=5142| accessdate = }}</ref>
| update_page = yes
| require_manual_inspection = no
| update_protein_box = yes
| update_summary = yes
| update_citations = yes
}}


<!-- The GNF_Protein_box is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
This gene is a member of the type IV, cyclic AMP (cAMP)-specific, cyclic nucleotide [[phosphodiesterase]] (PDE) family. Cyclic nucleotides are important second messengers that regulate and mediate a number of [[Cell (biology)|cell]]ular responses to extracellular signals, such as [[hormone]]s, [[light]], and [[neurotransmitter]]s. The [[cyclic nucleotide phosphodiesterase]]s (PDEs) regulate the cellular concentrations of cyclic nucleotides and thereby play a role in signal transduction. This gene encodes a protein that specifically hydrolyzes [[Cyclic adenosine monophosphate|cAMP]]. Alternate transcriptional splice variants, encoding different [[isoforms]], have been characterized.<ref name="entrez" /><ref>{{Cite book|title = Behavioral Neurobiology of Schizophrenia and Its Treatment|url = https://books.google.com/?id=udlELa8_6aoC&pg=PA643&dq=pde4b+gene#v=onepage&q=pde4b%20gene&f=false|publisher = Springer Science & Business Media|date = 2010-08-19|isbn = 9783642137174|first = Neal R.|last = Swerdlow}}</ref>
{{GNF_Protein_box
| image = PBB_Protein_PDE4B_image.jpg
| image_source = [[Protein_Data_Bank|PDB]] rendering based on 1f0j.
| PDB = {{PDB2|1f0j}}, {{PDB2|1ro6}}, {{PDB2|1ro9}}, {{PDB2|1ror}}, {{PDB2|1tb5}}, {{PDB2|1xlx}}, {{PDB2|1xlz}}, {{PDB2|1xm4}}, {{PDB2|1xm6}}, {{PDB2|1xmu}}, {{PDB2|1xmy}}, {{PDB2|1xn0}}, {{PDB2|1xos}}, {{PDB2|1xot}}, {{PDB2|1y2h}}, {{PDB2|1y2j}}
| Name = Phosphodiesterase 4B, cAMP-specific (phosphodiesterase E4 dunce homolog, Drosophila)
| HGNCid = 8781
| Symbol = PDE4B
| AltSymbols =; DKFZp686F2182; DPDE4; MGC126529; PDEIVB
| OMIM = 600127
| ECnumber = 
| Homologene = 1953
| MGIid = 99557
| GeneAtlas_image1 = PBB_GE_PDE4B_211302_s_at_tn.png
| GeneAtlas_image2 = PBB_GE_PDE4B_203708_at_tn.png
| GeneAtlas_image3 = PBB_GE_PDE4B_gnf1h03574_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:0005625 |text = soluble fraction}} {{GNF_GO|id=GO:0005626 |text = insoluble fraction}}
| Process = {{GNF_GO|id=GO:0007165 |text = signal transduction}}
| Orthologs = {{GNF_Ortholog_box
    | Hs_EntrezGene = 5142
    | Hs_Ensembl = ENSG00000184588
    | Hs_RefseqProtein = NP_001032416
    | Hs_RefseqmRNA = NM_001037339
    | Hs_GenLoc_db = 
    | Hs_GenLoc_chr = 1
    | Hs_GenLoc_start = 66030785
    | Hs_GenLoc_end = 66612850
    | Hs_Uniprot = Q07343
    | Mm_EntrezGene = 18578
    | Mm_Ensembl = ENSMUSG00000028525
    | Mm_RefseqmRNA = NM_019840
    | Mm_RefseqProtein = NP_062814
    | Mm_GenLoc_db = 
    | Mm_GenLoc_chr = 4
    | Mm_GenLoc_start = 101753153
    | Mm_GenLoc_end = 102103755
    | Mm_Uniprot = 
  }}
}}
'''Phosphodiesterase 4B, cAMP-specific (phosphodiesterase E4 dunce homolog, Drosophila)''', also known as '''PDE4B''', is a human [[gene]].<ref name="entrez">{{cite web | title = Entrez Gene: PDE4B phosphodiesterase 4B, cAMP-specific (phosphodiesterase E4 dunce homolog, Drosophila)| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=5142| accessdate = }}</ref>


<!-- The PBB_Summary template is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
==Clinical relevance==
{{PBB_Summary
| section_title =  
| summary_text = This gene is a member of the type IV, cyclic AMP (cAMP)-specific, cyclic nucleotide phosphodiesterase (PDE) family. Cyclic nucleotides are important second messengers that regulate and mediate a number of cellular responses to extracellular signals, such as hormones, light, and neurotransmitters. The cyclic nucleotide phosphodiesterases (PDEs) regulate the cellular concentrations of cyclic nucleotides and thereby play a role in signal transduction. This gene encodes a protein that specifically hydrolyzes cAMP. Altered activity of this protein has been associated with schizophrenia and bipolar affective disorder. Alternate transcriptional splice variants, encoding different isoforms, have been characterized.<ref name="entrez">{{cite web | title = Entrez Gene: PDE4B phosphodiesterase 4B, cAMP-specific (phosphodiesterase E4 dunce homolog, Drosophila)| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=5142| accessdate = }}</ref>
}}


==References==
Altered activity of this protein has been associated with [[schizophrenia]] and [[bipolar disorder]].<ref name = "entrez"/> PDE4B is believed to be the PDE4 subtype involved in the [[antipsychotic]] effects of [[PDE4 inhibitor]]s such as [[rolipram]].<ref>{{cite journal | vauthors = Porteous DJ, Millar JK, Brandon NJ, Sawa A | title = DISC1 at 10: connecting psychiatric genetics and neuroscience | journal = Trends in Molecular Medicine | volume = 17 | issue = 12 | pages = 699–706 | date = Dec 2011 | pmid = 22015021 | pmc = 3253483 | doi = 10.1016/j.molmed.2011.09.002 }}</ref> PDE4B is involved in [[dopamine]]-associated and stress-related behaviours.<ref>{{cite book | title = Phosphodiesterases as Drug Targets | series = Handbook of Experimental Pharmacology | volume=204 | date = 2011 | doi = 10.1007/978-3-642-17969-3 | isbn = 978-3-642-17968-6 | url = https://link.springer.com.elibrary.jcu.edu.au/content/pdf/10.1007%2F978-3-642-17969-3.pdf | format = PDF | publisher = Springer Berlin Heidelberg | editors = Francis, SH; Conti, M; Houslay, MD }}</ref> It has also recently been found to modulate cognition, as reduction in PDE4B activity improves memory and long-term plasticity in mouse models, possibly supporting further therapeutic applications.<ref>http://newsdaily.com/2015/08/scientists-researching-brain-disorders-create-super-clever-mice/</ref>
{{reflist|2}}
 
==Further reading==
== Inhibitors ==
{{refbegin | 2}}
 
{{PBB_Further_reading
[[AN2728]], a [[boron]]-containing drug candidate that as of 2015 was under development by [[Anacor]] Pharmaceuticals for the topical treatment of [[psoriasis]] and [[atopic dermatitis]] (atopic eczema).<ref name=Anacor>Anacor [http://www.anacor.com/an2728.php AN2728 at Anacor website] Page accessed May 15, 2015</ref><ref name=Nazarian>{{cite journal | vauthors = Nazarian R, Weinberg JM | title = AN-2728, a PDE4 inhibitor for the potential topical treatment of psoriasis and atopic dermatitis | journal = Current Opinion in Investigational Drugs | volume = 10 | issue = 11 | pages = 1236–42 | date = Nov 2009 | pmid = 19876791 }}</ref><ref name=Moustafa>{{cite journal | vauthors = Moustafa F, Feldman SR | date = May 2014 | title = A review of phosphodiesterase-inhibition and the potential role for phosphodiesterase 4-inhibitors in clinical dermatology | url = http://escholarship.org/uc/item/2hx1m6kv#page-1 | journal = Dermatol. Online J. | volume = 20 | issue = 5| page = 22608 | pmid = 24852768 }}</ref> mainly acting on PDE4B.<ref name=Moustafa/>
| citations =  
 
*{{cite journal  | author=Szpirer C, Szpirer J, Rivière M, ''et al.'' |title=Chromosomal localization of the human and rat genes (PDE4D and PDE4B) encoding the cAMP-specific phosphodiesterases 3 and 4. |journal=Cytogenet. Cell Genet. |volume=69 |issue= 1-2 |pages= 11-4 |year= 1995 |pmid= 7835077 |doi= }}
== References ==
*{{cite journal  | author=Bolger GB, Rodgers L, Riggs M |title=Differential CNS expression of alternative mRNA isoforms of the mammalian genes encoding cAMP-specific phosphodiesterases. |journal=Gene |volume=149 |issue= 2 |pages= 237-44 |year= 1994 |pmid= 7958996 |doi=  }}
{{reflist|33em}}
*{{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= }}
 
*{{cite journal | author=McLaughlin MM, Cieslinski LB, Burman M, ''et al.'' |title=A low-Km, rolipram-sensitive, cAMP-specific phosphodiesterase from human brain. Cloning and expression of cDNA, biochemical characterization of recombinant protein, and tissue distribution of mRNA. |journal=J. Biol. Chem. |volume=268 |issue= 9 |pages= 6470-6 |year= 1993 |pmid= 8384210 |doi=  }}
== Further reading ==
*{{cite journal | author=Obernolte R, Bhakta S, Alvarez R, ''et al.'' |title=The cDNA of a human lymphocyte cyclic-AMP phosphodiesterase (PDE IV) reveals a multigene family. |journal=Gene |volume=129 |issue= 2 |pages= 239-47 |year= 1993 |pmid= 8392015 |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 = Szpirer C, Szpirer J, Rivière M, Swinnen J, Vicini E, Conti M | title = Chromosomal localization of the human and rat genes (PDE4D and PDE4B) encoding the cAMP-specific phosphodiesterases 3 and 4 | journal = Cytogenetics and Cell Genetics | volume = 69 | issue = 1–2 | pages = 11–4 | year = 1995 | pmid = 7835077 | doi = 10.1159/000133927 }}
*{{cite journal | author=Huston E, Lumb S, Russell A, ''et al.'' |title=Molecular cloning and transient expression in COS7 cells of a novel human PDE4B cAMP-specific phosphodiesterase, HSPDE4B3. |journal=Biochem. J. |volume=328 ( Pt 2) |issue= |pages= 549-58 |year= 1998 |pmid= 9371714 |doi= }}
* {{cite journal | vauthors = Bolger GB, Rodgers L, Riggs M | title = Differential CNS expression of alternative mRNA isoforms of the mammalian genes encoding cAMP-specific phosphodiesterases | journal = Gene | volume = 149 | issue = 2 | pages = 237–44 | date = Nov 1994 | pmid = 7958996 | doi = 10.1016/0378-1119(94)90155-4 }}
*{{cite journal | author=Ma D, Wu P, Egan RW, ''et al.'' |title=Phosphodiesterase 4B gene transcription is activated by lipopolysaccharide and inhibited by interleukin-10 in human monocytes. |journal=Mol. Pharmacol. |volume=55 |issue= 1 |pages= 50-7 |year= 1999 |pmid= 9882697 |doi=  }}
* {{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 | doi = 10.1007/BF02290677 }}
*{{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 = McLaughlin MM, Cieslinski LB, Burman M, Torphy TJ, Livi GP | title = A low-Km, rolipram-sensitive, cAMP-specific phosphodiesterase from human brain. Cloning and expression of cDNA, biochemical characterization of recombinant protein, and tissue distribution of mRNA | journal = The Journal of Biological Chemistry | volume = 268 | issue = 9 | pages = 6470–6 | date = Mar 1993 | pmid = 8384210 | doi =  }}
*{{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 = Obernolte R, Bhakta S, Alvarez R, Bach C, Zuppan P, Mulkins M, Jarnagin K, Shelton ER | title = The cDNA of a human lymphocyte cyclic-AMP phosphodiesterase (PDE IV) reveals a multigene family | journal = Gene | volume = 129 | issue = 2 | pages = 239–47 | date = Jul 1993 | pmid = 8392015 | doi = 10.1016/0378-1119(93)90274-7 }}
*{{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 = 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 | doi = 10.1128/mcb.13.10.6558}}
*{{cite journal | author=Shepherd M, McSorley T, Olsen AE, ''et al.'' |title=Molecular cloning and subcellular distribution of the novel PDE4B4 cAMP-specific phosphodiesterase isoform. |journal=Biochem. J. |volume=370 |issue= Pt 2 |pages= 429-38 |year= 2003 |pmid= 12441002 |doi= 10.1042/BJ20021082 }}
* {{cite journal | vauthors = Huston E, Lumb S, Russell A, Catterall C, Ross AH, Steele MR, Bolger GB, Perry MJ, Owens RJ, Houslay MD | title = Molecular cloning and transient expression in COS7 cells of a novel human PDE4B cAMP-specific phosphodiesterase, HSPDE4B3 | journal = The Biochemical Journal | volume = 328 | issue = Pt 2 | pages = 549–58 | date = Dec 1997 | pmid = 9371714 | pmc = 1218954 | doi =  10.1042/bj3280549}}
*{{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 = Ma D, Wu P, Egan RW, Billah MM, Wang P | title = Phosphodiesterase 4B gene transcription is activated by lipopolysaccharide and inhibited by interleukin-10 in human monocytes | journal = Molecular Pharmacology | volume = 55 | issue = 1 | pages = 50–7 | date = Jan 1999 | pmid = 9882697 | doi = }}
*{{cite journal | author=Arp J, Kirchhof MG, Baroja ML, ''et al.'' |title=Regulation of T-cell activation by phosphodiesterase 4B2 requires its dynamic redistribution during immunological synapse formation. |journal=Mol. Cell. Biol. |volume=23 |issue= 22 |pages= 8042-57 |year= 2003 |pmid= 14585965 |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 | bibcode = 2000PNAS...9714620S }}
*{{cite journal | author=Ota T, Suzuki Y, Nishikawa T, ''et al.'' |title=Complete sequencing and characterization of 21,243 full-length human cDNAs. |journal=Nat. Genet. |volume=36 |issue= 1 |pages= 40-5 |year= 2004 |pmid= 14702039 |doi= 10.1038/ng1285 }}
* {{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 }}
*{{cite journal | author=Brandenberger R, Wei H, Zhang S, ''et al.'' |title=Transcriptome characterization elucidates signaling networks that control human ES cell growth and differentiation. |journal=Nat. Biotechnol. |volume=22 |issue= 6 |pages= 707-16 |year= 2005 |pmid= 15146197 |doi= 10.1038/nbt971 }}
* {{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 | doi = }}
*{{cite journal | author=Smith PG, Wang F, Wilkinson KN, ''et al.'' |title=The phosphodiesterase PDE4B limits cAMP-associated PI3K/AKT-dependent apoptosis in diffuse large B-cell lymphoma. |journal=Blood |volume=105 |issue= 1 |pages= 308-16 |year= 2005 |pmid= 15331441 |doi= 10.1182/blood-2004-01-0240 }}
* {{cite journal | vauthors = Shepherd M, McSorley T, Olsen AE, Johnston LA, Thomson NC, Baillie GS, Houslay MD, Bolger GB | title = Molecular cloning and subcellular distribution of the novel PDE4B4 cAMP-specific phosphodiesterase isoform | journal = The Biochemical Journal | volume = 370 | issue = Pt 2 | pages = 429–38 | date = Mar 2003 | pmid = 12441002 | pmc = 1223190 | doi = 10.1042/BJ20021082 }}
*{{cite journal | author=Ballif BA, Villén J, Beausoleil SA, ''et al.'' |title=Phosphoproteomic analysis of the developing mouse brain. |journal=Mol. Cell Proteomics |volume=3 |issue= 11 |pages= 1093-101 |year= 2005 |pmid= 15345747 |doi= 10.1074/mcp.M400085-MCP200 }}
* {{cite journal | vauthors = Arp J, Kirchhof MG, Baroja ML, Nazarian SH, Chau TA, Strathdee CA, Ball EH, Madrenas J | title = Regulation of T-cell activation by phosphodiesterase 4B2 requires its dynamic redistribution during immunological synapse formation | journal = Molecular and Cellular Biology | volume = 23 | issue = 22 | pages = 8042–57 | date = Nov 2003 | pmid = 14585965 | pmc = 262363 | doi = 10.1128/MCB.23.22.8042-8057.2003 }}
*{{cite journal | author=Millar JK, Pickard BS, Mackie S, ''et al.'' |title=DISC1 and PDE4B are interacting genetic factors in schizophrenia that regulate cAMP signaling. |journal=Science |volume=310 |issue= 5751 |pages= 1187-91 |year= 2005 |pmid= 16293762 |doi= 10.1126/science.1112915 }}
* {{cite journal | vauthors = Brandenberger R, Wei H, Zhang S, Lei S, Murage J, Fisk GJ, Li Y, Xu C, Fang R, Guegler K, Rao MS, Mandalam R, Lebkowski J, Stanton LW | title = Transcriptome characterization elucidates signaling networks that control human ES cell growth and differentiation | journal = Nature Biotechnology | volume = 22 | issue = 6 | pages = 707–16 | date = Jun 2004 | pmid = 15146197 | doi = 10.1038/nbt971 }}
*{{cite journal | author=Kimura K, Wakamatsu A, Suzuki Y, ''et al.'' |title=Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes. |journal=Genome Res. |volume=16 |issue= 1 |pages= 55-65 |year= 2006 |pmid= 16344560 |doi= 10.1101/gr.4039406 }}
* {{cite journal | vauthors = Smith PG, Wang F, Wilkinson KN, Savage KJ, Klein U, Neuberg DS, Bollag G, Shipp MA, Aguiar RC | title = The phosphodiesterase PDE4B limits cAMP-associated PI3K/AKT-dependent apoptosis in diffuse large B-cell lymphoma | journal = Blood | volume = 105 | issue = 1 | pages = 308–16 | date = Jan 2005 | pmid = 15331441 | doi = 10.1182/blood-2004-01-0240 }}
}}
* {{cite journal | vauthors = Ballif BA, Villén J, Beausoleil SA, Schwartz D, Gygi SP | title = Phosphoproteomic analysis of the developing mouse brain | journal = Molecular & Cellular Proteomics | volume = 3 | issue = 11 | pages = 1093–101 | date = Nov 2004 | pmid = 15345747 | doi = 10.1074/mcp.M400085-MCP200 }}
* {{cite journal | vauthors = Millar JK, Pickard BS, Mackie S, James R, Christie S, Buchanan SR, Malloy MP, Chubb JE, Huston E, Baillie GS, Thomson PA, Hill EV, Brandon NJ, Rain JC, Camargo LM, Whiting PJ, Houslay MD, Blackwood DH, Muir WJ, Porteous DJ | title = DISC1 and PDE4B are interacting genetic factors in schizophrenia that regulate cAMP signaling | journal = Science | volume = 310 | issue = 5751 | pages = 1187–91 | date = Nov 2005 | pmid = 16293762 | doi = 10.1126/science.1112915 | bibcode = 2005Sci...310.1187M }}
* {{cite journal | vauthors = Kimura K, Wakamatsu A, Suzuki Y, Ota T, Nishikawa T, Yamashita R, Yamamoto J, Sekine M, Tsuritani K, Wakaguri H, Ishii S, Sugiyama T, Saito K, Isono Y, Irie R, Kushida N, Yoneyama T, Otsuka R, Kanda K, Yokoi T, Kondo H, Wagatsuma M, Murakawa K, Ishida S, Ishibashi T, Takahashi-Fujii A, Tanase T, Nagai K, Kikuchi H, Nakai K, Isogai T, Sugano S | title = Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes | journal = Genome Research | volume = 16 | issue = 1 | pages = 55–65 | date = Jan 2006 | pmid = 16344560 | pmc = 1356129 | doi = 10.1101/gr.4039406 }}
{{refend}}
{{refend}}
 
{{PDB Gallery|geneid=5142}}
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Latest revision as of 22:30, 29 December 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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Location (UCSC)n/an/a
PubMed searchn/an/a
Wikidata
View/Edit Human

cAMP-specific 3',5'-cyclic phosphodiesterase 4B is an enzyme that in humans is encoded by the PDE4B gene.[1]

This gene is a member of the type IV, cyclic AMP (cAMP)-specific, cyclic nucleotide phosphodiesterase (PDE) family. Cyclic nucleotides are important second messengers that regulate and mediate a number of cellular responses to extracellular signals, such as hormones, light, and neurotransmitters. The cyclic nucleotide phosphodiesterases (PDEs) regulate the cellular concentrations of cyclic nucleotides and thereby play a role in signal transduction. This gene encodes a protein that specifically hydrolyzes cAMP. Alternate transcriptional splice variants, encoding different isoforms, have been characterized.[1][2]

Clinical relevance

Altered activity of this protein has been associated with schizophrenia and bipolar disorder.[1] PDE4B is believed to be the PDE4 subtype involved in the antipsychotic effects of PDE4 inhibitors such as rolipram.[3] PDE4B is involved in dopamine-associated and stress-related behaviours.[4] It has also recently been found to modulate cognition, as reduction in PDE4B activity improves memory and long-term plasticity in mouse models, possibly supporting further therapeutic applications.[5]

Inhibitors

AN2728, a boron-containing drug candidate that as of 2015 was under development by Anacor Pharmaceuticals for the topical treatment of psoriasis and atopic dermatitis (atopic eczema).[6][7][8] mainly acting on PDE4B.[8]

References

  1. ↑ 1.0 1.1 1.2 "Entrez Gene: PDE4B phosphodiesterase 4B, cAMP-specific (phosphodiesterase E4 dunce homolog, Drosophila)".
  2. ↑ Swerdlow, Neal R. (2010-08-19). Behavioral Neurobiology of Schizophrenia and Its Treatment. Springer Science & Business Media. ISBN 9783642137174.
  3. ↑ Porteous DJ, Millar JK, Brandon NJ, Sawa A (Dec 2011). "DISC1 at 10: connecting psychiatric genetics and neuroscience". Trends in Molecular Medicine. 17 (12): 699–706. doi:10.1016/j.molmed.2011.09.002. PMC 3253483. PMID 22015021.
  4. ↑ Francis, SH; Conti, M; Houslay, MD, eds. (2011). Phosphodiesterases as Drug Targets (PDF). Handbook of Experimental Pharmacology. 204. Springer Berlin Heidelberg. doi:10.1007/978-3-642-17969-3. ISBN 978-3-642-17968-6.
  5. ↑ http://newsdaily.com/2015/08/scientists-researching-brain-disorders-create-super-clever-mice/
  6. ↑ Anacor AN2728 at Anacor website Page accessed May 15, 2015
  7. ↑ Nazarian R, Weinberg JM (Nov 2009). "AN-2728, a PDE4 inhibitor for the potential topical treatment of psoriasis and atopic dermatitis". Current Opinion in Investigational Drugs. 10 (11): 1236–42. PMID 19876791.
  8. ↑ 8.0 8.1 Moustafa F, Feldman SR (May 2014). "A review of phosphodiesterase-inhibition and the potential role for phosphodiesterase 4-inhibitors in clinical dermatology". Dermatol. Online J. 20 (5): 22608. PMID 24852768.

Further reading

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