Recombinant Human 3',5'-cyclic-AMP phosphodiesterase 4A (PDE4A DPDE2)

1. FCPR16 is a novel PDE4 inhibitor with little emetic potential...Our findings indicate that FCPR16 is a promising pre-clinical candidate for the treatment of PD and possibly other oxidative stress-related neuronal diseases. PMID: 29475134
2. Here we describe a compound, BC54, that is a selective inhibitor of enzymes from the cAMP-specific PDE4 and PDE7 families. Consistent with the biological effect of other PDE4 and PDE7 inhibitors, BC54 displays potent anti-inflammatory properties and is superior to a combination of rolipram (a PDE4 inhibitor) and BRL50481 (a PDE7A inhibitor) for inducing apoptosis in chronic lymphocytic leukemia (CLL) cells PMID: 28867658
3. Repurposing the PDE4 inhibitor roflumilast for treatment of B-cell malignancies is safe, suppresses the oncogenic PI3K/AKT kinases, and may be clinically active PMID: 27542768
4. The expression of PDE4A4 and PDE4A8 in normal pituitary, their increased expression in adenomatous pituitary cells where AIP is meant to participate, and the disruption of the PDE4A4-AIP interaction by AIP mutants may play a role in pituitary tumorigenesis. PMID: 27267386
5. Low PDE4A expression is associated with sepsis. PMID: 28356347
6. Findings demonstrate loss of PDE4 expression in the striato-thalamo-cortical circuit, which is associated with deficits of spatial working memory in patients with Parkinson disease. PMID: 28701494
7. A multifunctional docking site on the catalytic unit of PDE4 that is utilized by multiple interaction partners has been identified. PMID: 27993970
8. After 48 h yessotoxin treatment PDE4A-dependent autophagy, as non-apoptotic programmed cell death, is activated. PMID: 25576684
9. AKAP 149-PKA-PDE4A complex localization is related with YTX effect in K-562 cell line PMID: 24813785
10. Hydroxycarbamide decreases sickle reticulocyte adhesion to resting endothelium by inhibiting endothelial lutheran/basal cell adhesion molecule (Lu/BCAM) through phosphodiesterase 4A activation. PMID: 24616094
11. long-acting beta -agonist and PDE4 inhibitor have a synergistic effect in regulating fibroblast tissue repair functions and PGE2 can modulate the effect of beta -agonist and PDE4 inhibitor at least in part through the mechanism of regulating PDE4 expression PMID: 24227907
12. The hPDE4 long isoforms are activated by phosphorylation of a serine located in a conserved RRESF motif in a tandem of N-terminal upstream-conserved regions (UCR). PMID: 22484154
13. PDE4A and PDE4C work in redundant fashion to mediate the loss of inhibitory PGE2 signaling in lung fibroblasts. PMID: 23043089
14. In phosphoinositide 3-kinasegamma-deficient cardiomyocytes, coincident signaling of the major cardiac PDE3 and PDE4 isoforms orchestrates a feedback loop that prevents calcium-dependent ventricular arrhythmia. PMID: 23008439
15. Data demonstrate that upregulation of Nox4 leads to an upregulation of PDE4A, B, and D and increased hydrolysis of cAMP which in turn augments cell replication and angiogenesis. PMID: 21732365
16. These results indicate that PDE4A and PLAT may be susceptibility genes for schizophrenia in the Japanese population. PMID: 21898905
17. PDE4 expression is reduced in failing human heart. PDE4 affects local but not global cAMP levels in human cardiomyocytes. PMID: 21161247
18. Data show that inhibition of PA hydrolysis provokes internalization of inactive EGFR, accompanied by a transient increase in PA levels and PDE4s activity. PMID: 20554760
19. The results of this study suggested that apPDE4s can participate in the regulation of cAMP signaling through specific subcellular localization by means of lipid binding activities. PMID: 20813835
20. GSK256066 demonstrated a protective effect on the EAR and LAR. PMID: 20193079
21. The results suggest that brain-derived neurotrophic factor/TrkB and cAMP phosphodiesterase-4, but not the gastrin-releasing peptide receptor, regulate the viability of medulloblastoma cells. PMID: 19642024
22. Inhibition of PDE4 inhibition (rather than PDE3) may diminish proliferation of human lung fibroblasts and therefore could be useful in the therapy of pathological remodeling in lung diseases. PMID: 20082309
23. Data show that PI3K activation and PIP3 production lead to recruitment of the PKB/beta-arrestin/PDE4 complex to the membrane via the PKB PH domain, resulting in degradation of the TCR-induced cAMP pool and allowing full T-cell activation to proceed. PMID: 20086095
24. Results suggest that TGF-beta1 mediated up-regulation of phosphodiesterase 4 promotes epithelial-mesenchymal transition in alveolar epithelial cells. PMID: 19759179
25. In vitro phosphorylation of PDE4A4 by the PKA-catalytic subunit increases the enzyme's sensitivity to Mg(2+), leading to 4-fold increased cAMP hydrolysis without affecting its K(m). PMID: 11852080
26. Results suggest that type 4A cAMP-specific phosphodiesterase may downregulate cyclic AMP signaling at the cell membrane and/or in the extracellular space at the time of granule release. PMID: 12764607
27. PDE4A11 is a novel, widely expressed long isoform that is activated by protein kinase A phosphorylation, shows a distinct intracellular localization, and may contribute to compartmentalized cyclic AMP signaling in cells in which it is expressed. PMID: 15738310
28. In this review, the fundamental biological role of PDE4 in intracellular signalling, its tissue distribution and regulation are described. PMID: 16300476
29. unique tissue distribution of PDE4A8, combined with the evolutionary divergence of its N-terminus, suggest that this isoform may have a specific function in regulating cAMP levels in human skeletal muscle and brain PMID: 18095939
30. observed that specific isoforms of PDE4A were reduced in cerebella of patients with bipolar disorder, whereas there was no change in patients with schizophrenia or major depression PMID: 19018233
31. PDE4 is widely expressed in brain tumors and promotes their growth PMID: 19047098
32. An 11-residue helical module in the N-terminal region of PDE4A1 determines the association with phospholipid bilayers and shows a profound selectivity for interaction with phosphatidic acid. PMID: 11994273
33. The immunophilin AIP (XAP2/ARA9) reversibly inhibited the enzymatic activity of PDE4A5, an isoform of PDE4A. PMID: 12810716
34. PDE4A10 is a long form splice variant of the human cAMP phosphodiesterase PDE4A gene. PDE4A10 was localized primarily to the perinuclear region of COS7 cells. PMID: 11306681
35. The unique N-terminal region of PDE4A1 consists of two helices, where Helix-1 regulates the phospholipase-D-dependent redistribution of PDE4A1 in response to release of Ca2+, providing a unique link between these signalling pathways PMID: 16940352
36. The N-terminal region unique to PDE4A1 consists of two well-defined helical regions separated by a mobile hinge region. Helix-2 provides the core membrane-insertion module and helix-1 facilitates membrane association. PMID: 16856845
37. PDE4A4 is specifically up-regulated in macrophages from smokers with chronic obstructive pulmonary disease (COPD) and may provide a specific therapeutic target. PMID: 15047569
38. PDE4A4 interacts with the p75 neurotropin receptor to enhance cAMP degradation and block fibrinolysis by down-regulating tissue plasminogen activator and so perpetuating scar formation after sciatic nerve and lung injury PMID: 17576803
39. Keynote review: phosphodiesterase-4 as a therapeutic target PMID: 16257373
40. purification and characterization of recombinant proteins from E coli and Sf9 cells PMID: 11566027

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HGNC: 8780

OMIM: 600126

KEGG: hsa:5141

STRING: 9606.ENSP00000270474

UniGene: Hs.89901