PDE4B

Last updated
PDE4B
Protein PDE4B PDB 1f0j.png
Available structures
PDB Human UniProt search: PDBe RCSB
Identifiers
Aliases PDE4B , DPDE4, PDEIVB, phosphodiesterase 4B
External IDs OMIM: 600127 MGI: 99557 HomoloGene: 1953 GeneCards: PDE4B
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)
RefSeq (protein)

n/a

Location (UCSC) Chr 1: 65.79 – 66.37 Mb Chr 4: 101.94 – 102.46 Mb
PubMed search [3] [4]
Wikidata
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cAMP-specific 3',5'-cyclic phosphodiesterase 4B is an enzyme that in humans is encoded by the PDE4B gene. [5]

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. [5] [6]

Clinical relevance

Altered activity of this protein has been associated with schizophrenia and bipolar disorder. [5] PDE4B is believed to be the PDE4 subtype involved in the antipsychotic effects of PDE4 inhibitors such as rolipram. [7] PDE4B is involved in dopamine-associated and stress-related behaviours. [8] 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. [9]

Inhibitors

Crisaborole, a boron-containing drug was approved by the FDA in 2016 for the treatment of atopic dermatitis, and as of 2024 is being commercialized by Pfizer under the name of Eucrisa (chemical name: 4-[(1-hydroxy-1,3-dihydro-2,1-benzoxaborol-5-yl)oxy]benzonitrile) mainly acting on PDE4B. [10] [11] [12]

Related Research Articles

<span class="mw-page-title-main">Phosphodiesterase inhibitor</span> Drug

A phosphodiesterase inhibitor is a drug that blocks one or more of the five subtypes of the enzyme phosphodiesterase (PDE), thereby preventing the inactivation of the intracellular second messengers, cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) by the respective PDE subtype(s). The ubiquitous presence of this enzyme means that non-specific inhibitors have a wide range of actions, the actions in the heart, and lungs being some of the first to find a therapeutic use.

<span class="mw-page-title-main">Cyclic nucleotide</span> Cyclic nucleic acid

A cyclic nucleotide (cNMP) is a single-phosphate nucleotide with a cyclic bond arrangement between the sugar and phosphate groups. Like other nucleotides, cyclic nucleotides are composed of three functional groups: a sugar, a nitrogenous base, and a single phosphate group. As can be seen in the cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) images, the 'cyclic' portion consists of two bonds between the phosphate group and the 3' and 5' hydroxyl groups of the sugar, very often a ribose.

<span class="mw-page-title-main">Phosphodiesterase</span> Class of enzymes

A phosphodiesterase (PDE) is an enzyme that breaks a phosphodiester bond. Usually, phosphodiesterase refers to cyclic nucleotide phosphodiesterases, which have great clinical significance and are described below. However, there are many other families of phosphodiesterases, including phospholipases C and D, autotaxin, sphingomyelin phosphodiesterase, DNases, RNases, and restriction endonucleases, as well as numerous less-well-characterized small-molecule phosphodiesterases.

<span class="mw-page-title-main">Cyclic nucleotide phosphodiesterase</span> Class of enzymes

3′,5′-cyclic-nucleotide phosphodiesterases (EC 3.1.4.17) are a family of phosphodiesterases. Generally, these enzymes hydrolyze a nucleoside 3′,5′-cyclic phosphate to a nucleoside 5′-phosphate:

<span class="mw-page-title-main">Phosphodiesterase 3</span> Class of enzymes

PDE3 is a phosphodiesterase. The PDEs belong to at least eleven related gene families, which are different in their primary structure, substrate affinity, responses to effectors, and regulation mechanism. Most of the PDE families are composed of more than one gene. PDE3 is clinically significant because of its role in regulating heart muscle, vascular smooth muscle and platelet aggregation. PDE3 inhibitors have been developed as pharmaceuticals, but their use is limited by arrhythmic effects and they can increase mortality in some applications.

Phosphodiesterase 1, PDE1, EC 3.1.4.1, systematic name oligonucleotide 5-nucleotidohydrolase) is a phosphodiesterase enzyme also known as calcium- and calmodulin-dependent phosphodiesterase. It is one of the 11 families of phosphodiesterase (PDE1-PDE11). Phosphodiesterase 1 has three subtypes, PDE1A, PDE1B and PDE1C which divide further into various isoforms. The various isoforms exhibit different affinities for cAMP and cGMP.

<span class="mw-page-title-main">PDE4D</span> Protein-coding gene in the species Homo sapiens

cAMP-specific 3',5'-cyclic phosphodiesterase 4D is an enzyme that in humans is encoded by the PDE4D gene.

<span class="mw-page-title-main">Receptor for activated C kinase 1</span> Protein-coding gene in the species Homo sapiens

Receptor for activated C kinase 1 (RACK1), also known as guanine nucleotide-binding protein subunit beta-2-like 1 (GNB2L1), is a 35 kDa protein that in humans is encoded by the RACK1 gene.

<span class="mw-page-title-main">PDE4A</span> Protein-coding gene in the species Homo sapiens

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

<span class="mw-page-title-main">PDE11A</span> Protein-coding gene in the species Homo sapiens

Dual 3',5'-cyclic-AMP and -GMP phosphodiesterase 11A is an enzyme that in humans is encoded by the PDE11A gene.

<span class="mw-page-title-main">PDE1A</span> Protein-coding gene in the species Homo sapiens

Calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1A is an enzyme that in humans is encoded by the PDE1A gene.

<span class="mw-page-title-main">PDE7A</span> Protein-coding gene in the species Homo sapiens

High affinity cAMP-specific 3',5'-cyclic phosphodiesterase 7A is an enzyme that in humans is encoded by the PDE7A gene. Mammals possess 21 cyclic nucleotide phosphodiesterase (PDE) genes that are pharmacologically grouped into 11 families. PDE7A is one of two genes in the PDE7 family, the other being PDE7B. The PDE7 family, along with the PDE4 and PDE8 families, are cAMP-specific, showing little to no activity against 3', 5'-cyclic guanosine monophosphate (cGMP).

<span class="mw-page-title-main">PDE4C</span> Protein-coding gene in the species Homo sapiens

cAMP-specific 3',5'-cyclic phosphodiesterase 4C is an enzyme that in humans is encoded by the PDE4C gene.

<span class="mw-page-title-main">PDE10A</span> Enzyme and protein-coding gene in humans

cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A is an enzyme that in humans is encoded by the PDE10A gene.

<span class="mw-page-title-main">PDE8B</span> Protein-coding gene in the species Homo sapiens

High affinity cAMP-specific and IBMX-insensitive 3',5'-cyclic phosphodiesterase 8B is an enzyme that in humans is encoded by the PDE8B gene.

<span class="mw-page-title-main">2',3'-Cyclic-nucleotide 3'-phosphodiesterase</span> Protein-coding gene in the species Homo sapiens

2′,3′-Cyclic-nucleotide 3'-phosphodiesterase is an enzyme that in humans is encoded by the CNP gene.

<span class="mw-page-title-main">Phosphodiesterase-4 inhibitor</span> Class of chemical compounds

A phosphodiesterase-4 inhibitor, commonly referred to as a PDE4 inhibitor, is a drug used to block the degradative action of phosphodiesterase 4 (PDE4) on cyclic adenosine monophosphate (cAMP). It is a member of the larger family of PDE inhibitors. The PDE4 family of enzymes are the most prevalent PDE in immune cells. They are predominantly responsible for hydrolyzing cAMP within both immune cells and cells in the central nervous system.

<span class="mw-page-title-main">Piclamilast</span> Chemical compound

Piclamilast, is a selective PDE4 inhibitor. It is comparable to other PDE4 inhibitors for its anti-inflammatory effects. It has been investigated for its applications to the treatment of conditions such as chronic obstructive pulmonary disease, bronchopulmonary dysplasia and asthma. It is a second generation compound that exhibits structural functionalities of the PDE4 inhibitors cilomilast and roflumilast. The structure for piclamilast was first elucidated in a 1995 European patent application. The earliest mention of the name "piclamilast" was used in a 1997 publication.

3′,5′-cyclic-AMP phosphodiesterase (EC 3.1.4.53, cAMP-specific phosphodiesterase, cAMP-specific PDE, PDE1, PDE2A, PDE2B, PDE4, PDE7, PDE8, PDEB1, PDEB2) is an enzyme with systematic name 3′,5′-cyclic-AMP 5′-nucleotidohydrolase. It catalyses the following reaction

<span class="mw-page-title-main">Cyclic di-AMP</span> Chemical compound

Cyclic di-AMP is a second messenger used in signal transduction in bacteria and archaea. It is present in many Gram-positive bacteria, some Gram-negative species, and archaea of the phylum euryarchaeota.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000184588 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000028525 - Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. 1 2 3 "Entrez Gene: PDE4B phosphodiesterase 4B, cAMP-specific (phosphodiesterase E4 dunce homolog, Drosophila)".
  6. Swerdlow, Neal R. (2010-08-19). Behavioral Neurobiology of Schizophrenia and Its Treatment. Springer Science & Business Media. ISBN   9783642137174.
  7. 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.
  8. Francis, SH; Conti, M; Houslay, MD, eds. (2011). Phosphodiesterases as Drug Targets (PDF). Handbook of Experimental Pharmacology. Vol. 204. Springer Berlin Heidelberg. doi:10.1007/978-3-642-17969-3. ISBN   978-3-642-17968-6.[ permanent dead link ]
  9. "Scientists researching brain disorders create super-clever mice | NewsDaily". Archived from the original on 2015-08-20. Retrieved 2015-08-21.
  10. "Eucrisa (crisaborole) Ointment". U.S. Food and Drug Administration (FDA). 23 January 2017. Retrieved 28 April 2020.
  11. 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.
  12. 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. doi: 10.5070/D3205022608 . PMID   24852768.

Further reading