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Mouse (Murine) phosphodiesterase 4D, cAMP-Specific (PDE4D) interaction partners

1. These results indicate that Phosphodiesterase-4D overexpression may be involved in the development of surgery-induced cognitive dysfunction in mice.

2. The effect of dobutamine as a positive inotrope is impaired in mice with cecal ligation and puncture-induced sepsis without changes in cardiac beta1-adrenoceptor signaling as a result of cAMP breakdown achieved by upregulated phosphodiesterase 4D

3. In vivo knockdown of PDE4D5 inhibited inflammation at athero-prone sites

4. Results indicate that the cyclic AMP (cAMP) increase is caused by the attenuation of phosphodiesterase (PDE) activity adrenal cortex-derived Y-1 cell line.

5. The authors demonstrate that the Attention Deficit Disorder with Hyperactivity phenotype depends on a dysregulation of CREB signaling exerted by a kinase-independent PI3Kgamma-PDE4D interaction in the noradrenergic neurons of the locus coeruleus.

6. SIK1 serves as a part of a self-regulatory circuit to modulate insulin secretion from pancreatic beta-cells by controlling cAMP concentration through modulation of PDE4D activity.

7. Cytokine-induced iNOS and ERK1/2 inhibit adenylyl cyclase type 5/6 activity and stimulate phosphodiesterase 4D5 activity in intestinal longitudinal smooth muscle, contributing to colonic dysmotility during inflammation.

8. the loss of function of either DISC1 or ATF4 increases PDE4D9 transcription, and the association of DISC1 with the PDE4D9 locus requires ATF4

9. these results suggest that Pde4d might serve specific biological functions in regulating the development process of the mouse embryo, and that CpG methylation of the Pde4d promoter may play an important role in regulating Pde4d at a transcriptional level.

10. Calcineurin regulates degradation of phosphodiesterase 3B, in addition to phosphodiesterase 4D.

11. Beta-arrestin-2 scaffolding of phosphodiesterase PDE4D5 to the plasma membrane was required for TRPV1 desensitization.

12. Phosphodiesterase 4D regulates baseline sarcoplasmic reticulum Ca2+ release and cardiac contractility, independently of L-type Ca2+ current.

13. Results identify PDE4B in the CaV1.2 complex as a critical regulator of ICa during beta-AR stimulation and suggest that distinct PDE4 subtypes are important for normal regulation of calcium-induced calcium release in cardiomyocytes.

14. Findings demonstrate that PDE4D and PDE4B have specialized functions in mouse embryonic fibroblasts with PDE4B controlling cAMP in a discrete subdomain near the plasma membrane.

15. The present results suggest that PDE4D, in particular long-form PDE4D, plays a critical role in the mediation of memory and hippocampal neurogenesis, which are mediated by cAMP/CREB signaling.

16. results suggest a novel regulatory mechanism for mTORC1 in which the cAMP-determined dynamic interaction between Rheb and PDE4D provides a key, unique regulatory event, and propose a new role for PDE4 as a molecular transducer for cAMP signaling.

17. PDE4D3, like protein kinase A and protein phosphatase 1, is recruited to the I(Ks) channel via AKAP-9 and contributes to its critical regulation by cAMP.

18. Results identify a novel signaling process governing G-protein-coupled cAMP signal transduction-opposing actions of the phosphatase calcineurin and the CK1/GSK3beta protein kinases on the phosphodegron-dependent degradation of PDE4D.

19. Activation of phosphodiesterase 4D constrains myocardial contractility via a ss2 adrenergic receptor-coupled phosphoinositide 3-kinase mechanism.

20. Reported here the cloning and characterization of a novel PDE4D isoform, PDE4D7.

Human phosphodiesterase 4D, cAMP-Specific (PDE4D) interaction partners

1. This study found that phosphodiesterase-4D7 gene added extra information to the available clinical data and conclude that the measurement of this gene in tumor tissue may contribute to more effective treatment decisions.Its score may support the risk stratification of patients after local treatment to select the right timing for the start of secondary therapy for men at very high-risk of rapid disease recurrence.

2. meta-analysis demonstrated that the SNP83 polymorphism in the PDE4D gene might contribute to ischemic stroke susceptibility especially in Asian populations[meta-analysis]

3. PDE4D polymorphism is associated with Gastric and esophageal cancer.

4. In Pseudohypoparathyroidism, mutations were found in PRKAR1A, PDE4D, TRPS1, and PTHLH.

5. TT genotype of SNP87 in PDE4D was associated with an increased risk for 3-month unfavorable outcome after total ischemic stroke, as well as stroke due to large-artery atherosclerosis and small-artery occlusion, in a Chinese population.

6. SNP 83 of PDE4D gene may increase the risk for developing ischemic stroke whereas SNP 87 and SNP45 of PDE4D may not be associated with the risk of ischemic stroke in the North Indian population

7. Results provide new information concerning the mechanism whereby the mutations identified in the ACRDYS2 dysregulate PDE4D activity, and give insights into rare diseases involving the cAMP signaling pathway.

8. This supports PDE4D5 and RACK1 as potential regulators of cell adhesion, spreading and migration through the non-classical exchange protein activated by cyclic AMP (EPAC1)/Rap1 signalling route

9. PDE4D isoform composition is altered in localized prostate cancer and it can be used both as a diagnostic as well as a prognostic biomarker.

10. Genetic analysis identified the identical, novel heterozygous missense mutation of the PDE4D gene c.569C>T (p.Ser190Phe) in two patients in same family. This case illustrates the significant phenotypic variability of acrodysostosis even within one family with identical mutations.

11. The key residues involved in the interaction with a number of in-house catechol iminoether derivatives, acting as PDE4DIs.

12. Screening of PRKAR1A and PDE4D in a Large Italian Series of Patients Clinically Diagnosed With Albright Hereditary Osteodystrophy and/or Pseudohypoparathyroidism

13. p53 induced the transcription of miR-139-5p, which in turn suppressed the protein levels of phosphodiesterase 4D (PDE4D), an oncogenic protein involved in multiple tumor promoting processes.

14. High PDE4D expression is associated with melanoma.

15. cells on fibronectin suppressed cAMP via enhanced phosphodiesterase (PDE) activity, through direct binding of integrin alpha5 to phosphodiesterase-4D5

16. we performed a meta-analysis of 15 studies, involving 8731 IS patients and 10,756 controls. The results showed nonsignificant association between PDE4D SNP56 and IS risk (T vs. A: OR=1.01, 95%CI=0.88-1.15, P=0.90). Similarly, in the subgroup analysis by ethnicity, no significant association was observed in Asian (T vs. A: OR=1.08, 95%CI=0.80-1.44, P=0.62) or European (T vs. A: OR=0.96, 95%CI=0.86-1.08, P=0.54) population.

17. Results support an important association of rs966221 and rs12188950 minor allele and its interaction with increased risk of ischemic stroke risk, and additional interaction between rs966221 and smoking

18. RACK1 and beta-arrestin2 inhibit the dimerization of PDE4D5.

19. PDE4D acts to allow cAMP-elevating agents to regulate VECADs' role as a sensor of flow-associated fluid shear stress (FSS)-encoded information in arterial endothelial cells.

20. PDE4D gene polymorphisms influence the susceptibility for the development of Sudden Sensorineural Hearing Loss in the southern Taiwanese female population.

Cow (Bovine) phosphodiesterase 4D, cAMP-Specific (PDE4D) interaction partners

1. demonstrate the presence of PDE4D transcript and protein, but also show an active enzyme, suggesting a functional role of PDE4D in bovine mammary gland