PDE4A

  • Official Full Name

    PDE4A phosphodiesterase 4A, cAMP-specific

  • Overview

    Cyclic nucleotide phosphodiesterases (PDEs) catalyse the hydrolytic inactivation of the common intracellular second messengers cyclic adenosine and guanosine 3, 5monophosphate (cAMP and cGMP). Thus, these enzymes play a critical role in the regulation of a wide range of physiological processes modulated by cyclic nucleotide signalling. The PDE4 enzyme belongs to a family of cAMPdependent PDEs that provide the major means of inactivating the key intracellular second messenger, cAMP. Four genes (4A, 4B, 4C, and 4D) encode around 20 distinct isoform members of the PDE4 family. Each isoform is characterized by a unique Nterminal region
  • Synonyms

    PDE4A; phosphodiesterase 4A, cAMP-specific; DPDE2, phosphodiesterase 4A, cAMP specific (dunce (Drosophila) homolog phosphodiesterase E2); cAMP-specific 3,5-cyclic phosphodiesterase 4A; phosphodiesterase E2 dunce homolog (Drosophila); phosphodiesterase isozyme 4; phosphodiesterase 4A, cAMP-specific (dunce; phosphodiesterase E2 dunce homolog, Drosophila; PDE4; DPDE2; PDE46;

  • Recombinant Proteins
  • Cell & Tissue Lysates
  • Protein Pre-coupled Magnetic Beads
  • Assay Kits
  • Human
  • Mouse
  • Rat
  • HEK293
  • HEK293T
  • In Vitro Cell Free System
  • Mammalian Cell
  • Sf9 Insect Cell
  • Wheat Germ
  • GST
  • His
  • His (Fc)
  • Avi
  • Myc
  • DDK
  • N/A
Species Cat.# Product name Source (Host) Tag Protein Length Price
Human PDE4A-1527H Active Recombinant Human PDE4A, GST-tagged Sf9 Insect Cell GST 332 aa-end
Human PDE4A-29933TH Recombinant Human PDE4A Wheat Germ N/A 647 amino acids
Human PDE4A-475H Recombinant Human PDE4A, GST-tagged, Active Sf9 Insect Cell GST
Human PDE4A-3352HCL Recombinant Human PDE4A 293 Cell Lysate HEK293 N/A
Human PDE4A6948H Recombinant Human PDE4A (352-685).docx Protein
Human PDE4A-366HF Recombinant Full Length Human PDE4A Protein In Vitro Cell Free System 647 amino acids
Mouse PDE4A-12553M Recombinant Mouse PDE4A Protein Mammalian Cell His
Mouse Pde4a-4745M Recombinant Mouse Pde4a Protein, Myc/DDK-tagged HEK293T Myc/DDK
Mouse PDE4A-6584M Recombinant Mouse PDE4A Protein, His (Fc)-Avi-tagged HEK293 His (Fc)-Avi
Mouse PDE4A-6584M-B Recombinant Mouse PDE4A Protein Pre-coupled Magnetic Beads HEK293
Rat PDE4A-4330R Recombinant Rat PDE4A Protein Mammalian Cell His
Rat PDE4A-3990R Recombinant Rat PDE4A Protein, His (Fc)-Avi-tagged HEK293 His (Fc)-Avi
Rat PDE4A-3990R-B Recombinant Rat PDE4A Protein Pre-coupled Magnetic Beads HEK293
Kit-1838 PDE4A Assay Kit N/A
  • Background
  • Case Study
  • Involved Pathway
  • Protein Function
  • Interacting Protein
  • Other Resource

What is PDE4A protein?

PDE4A (phosphodiesterase 4A) gene is a protein coding gene which situated on the short arm of chromosome 19 at locus 19p13. The PDE4 enzyme belongs to a family of cAMPdependent PDEs that provide the major means of inactivating the key intracellular second messenger, cAMP. Four genes (4A, 4B, 4C, and 4D) encode around 20 distinct isoform members of the PDE4 family. The gene encodes one member of PDE4 family. The PDE4A protein is consisted of 886 amino acids and its molecular mass is approximately 98.1 kDa.

What is the function of PDE4A protein?

The PDE4A protein belongs to the cyclic nucleotide phosphodiesterase (PDE) family, and PDE4 subfamily. This PDE hydrolyzes the second 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.

PDE4A-7.jpg

Fig1. Proposed model for the role of p75NTR in the cAMP-mediated plasminogen activation. (Benjamin D Sachs, 2007)

PDE4A Related Signaling Pathway

PDE4A is mainly involved in the regulation of cAMP (cyclic adenosine phosphate) signaling pathway. By specifically degrading cAMP, PDE4A regulates the concentration and duration of cAMP, and affects the downstream signal transduction of cAMP. In addition, PDE4A also interacts with other signaling pathways, such as MAPK/ERK, PI3K/AKT, and Wnt/β-catenin, which play important roles in cell growth, survival, and stress response.

PDE4A Related Diseases

PDE4A plays a key role in cardiovascular disease, including heart failure, myocardial infarction and hypertension. In addition, PDE4A has also been linked to neurological disorders such as Alzheimer's disease and Parkinson's disease. In these diseases, overactivation of PDE4A may lead to neuronal damage and death. Finally, PDE4A is also implicated in certain cancers because it can regulate the proliferation and survival of cancer cells.

Bioapplications of PDE4A

The most significant application of PDE4A is as a drug target. It is also used in clinical diagnosis, such as as a biomarker for certain inflammatory diseases to help doctors diagnose and monitor the disease.

Case study 1: Wito Richter, 2011

PDE4 isoenzymes are critical in the control of cAMP signaling in rodent cardiac myocytes. Ablation of PDE4 affects multiple key players in excitation-contraction coupling and predisposes mice to the development of heart failure. As little is known about PDE4 in human heart, the researchers explored to what extent cardiac expression and functions of PDE4 are conserved between rodents and humans. They find considerable similarities including comparable amounts of PDE4 activity expressed, expression of the same PDE4 subtypes and splicing variants, anchoring of PDE4 to the same subcellular compartments and macromolecular signaling complexes, and downregulation of PDE4 activity and protein in heart failure. As a consequence, the effect of PDE4 inactivation is different in rodents and humans. PDE4 inhibition leads to increased phosphorylation of virtually all PKA substrates in mouse cardiomyocytes, but increased phosphorylation of only a restricted number of proteins in human cardiomyocytes. These findings suggest that PDE4s have a similar role in the local regulation of cAMP signaling in rodent and human heart. However, inhibition of PDE4 has 'global' effects on cAMP signaling only in rodent hearts, as PDE4 comprises a large fraction of the total cardiac PDE activity in rodents but not in humans.

PDE4A-1.jpg

Fig1. Expression of PDE4 subtypes in rodent and human heart.

PDE4A-2.jpg
Fig2. Detection of macromolecular signaling complexes involving PDE4 in the human heart.

Case study 2: Ewa Kolosionek, 2009

Epithelial-mesenchymal transition (EMT) has emerged as a critical event in the pathogenesis of organ fibrosis and cancer and is typically induced by the multifunctional cytokine transforming growth factor (TGF)-beta1. The present study was undertaken to evaluate the potential role of phosphodiesterases (PDEs) in TGF-beta1-induced EMT in the human alveolar epithelial type II cell line A549. Interestingly, TGF-beta1 stimulation caused twofold increase in total cAMP-PDE activity, contributed mostly by PDE4. Furthermore, mRNA and protein expression demonstrated up-regulation of PDE4A and PDE4D isoforms in TGF-beta1-stimulated cells. And the ectopic overexpression of PDE4A and/or PDE4D resulted in a significant loss of epithelial marker E-cadherin but did not result in changes of mesenchymal markers. Collectively, the findings presented herein suggest that TGF-beta1 mediated up-regulation of PDE4 promotes EMT in alveolar epithelial cells.

PDE4A-3.jpg

Fig3. siRNA-mediated knockdown of PDE4A and PDE4D.

PDE4A-4.jpg
Fig4. Effects of PDE4 overexpression in inducing epithelial mesenchymal transition.
PDE4A-5.jpg

Fig1. Proposed functions of AIP in the pituitary gland and role of its interaction with PDEs. (Laura C Hernández-Ramírez, 2017)

PDE4A-6.jpg

Fig2. Schema of global activity of PGE2 activated PDE4 enzymes on multiple cAMP-coupled pathways. (Joel Michalski, 2012)

PDE4A involved in several pathways and played different roles in them. We selected most pathways PDE4A participated on our site, such as Purine metabolism, cAMP signaling pathway, which may be useful for your reference. Also, other proteins which involved in the same pathway with PDE4A were listed below. Creative BioMart supplied nearly all the proteins listed, you can search them on our site.

Pathway Name Pathway Related Protein
Purine metabolismENTPD2A.1;AMPD1;GUCY2E;NME6;ENPP4;POLR3F;XDH;PDE4D;ZNRD1
cAMP signaling pathwayATP1B3;CNGA1;FXYD1;GIPR;FFAR2;GRIN2D;CAMK2A;ACOX1;NFKBIA

PDE4A has several biochemical functions, for example, 3,5-cyclic-AMP phosphodiesterase activity, cAMP binding, metal ion binding. Some of the functions are cooperated with other proteins, some of the functions could acted by PDE4A itself. We selected most functions PDE4A had, and list some proteins which have the same functions with PDE4A. You can find most of the proteins on our site.

Function Related Protein
3,5-cyclic-AMP phosphodiesterase activityTDP2B;PDE4C;PDE7B;PDE3A;PDE4A;PDE8B;PDE4B;PDE1B;USB1
cAMP bindingRAPGEF3;PDE11A;PRKAR1A;PRKAR2B;CNGA4;POPDC2;RAPGEF4;PDE4B;CNGA2
metal ion bindingPDP2;CYP46A1.2;PRICKLE2B;FYN;ZFY1;ARID2;ATP8B5;ZFP354A;PVALB8
protein bindingSRGN;DZIP3;NKX2-1;COL6A2;RGS7BP;TRIM55;LMO2;ZWILCH;IGFLR1

PDE4A has direct interactions with proteins and molecules. Those interactions were detected by several methods such as yeast two hybrid, co-IP, pull-down and so on. We selected proteins and molecules interacted with PDE4A here. Most of them are supplied by our site. Hope this information will be useful for your research of PDE4A.

Dlg4; bosutinib; dasatinib; ITPKB

Research Area

Related articles

Uckert, S; Waldkirch, ES; et al. Expression and Distribution of Phosphodiesterase Isoenzymes in the Human Seminal Vesicles. JOURNAL OF SEXUAL MEDICINE 8:3058-3065(2011).
Richter, W; Jin, SLC; et al. Splice variants of the cyclic nucleotide phosphodiesterase PDE4D are, differentially expressed and regulated in rat tissue. BIOCHEMICAL JOURNAL 388:803-811(2005).
  • Reviews
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Customer Reviews (3)

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Reviews
12/05/2022

    PDE4A requires less storage environment.

    07/26/2022

      The expression of PDE4A was stable.

      02/08/2022

        It has the advantage of easy operation in the expression system and can improve the expression efficiency.

        Q&As (6)

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        How effective are PDE4A inhibitors in the treatment of asthma? 04/12/2022

        The inhibitors have been used in the treatment of asthma, and studies have shown that they can significantly reduce the number of asthma attacks and the use of drug D.

        How to introduce the structure of PDE4A? 03/30/2022

        This protein has multiple conserved regions and different subtypes, which is of great significance for the selective inhibition of drugs.

        What is a selective PDE4A inhibitor? 12/25/2021

        Selective PDE4A inhibitors refer to drug molecules that target only the PDE4A protein and do not inhibit other PDE4 homologs.

        What is the mechanism by which PDE4A regulates T cell-mediated autoimmune responses? 05/30/2021

        It plays an important role in the activation and regulation of T cells by regulating cAMP levels, and is involved in T cell-mediated autoimmune responses.

        Are levels of PDE4A associated with sleep disturbances? 02/12/2021

        Studies have shown that PDE4A depletion may be related to sleep-wake behavior and time stress response, but its specific role needs to be further studied.

        What is the expression pattern of PDE4A in T cells? 08/27/2020

        In T cells, PDE4A is mainly expressed in the cytoplasm and peripheral regions of the nuclear membrane.

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