Cyclic AMP-dependent phosphodiesterase type D (PDE4D) family is comprise of 5 variants (PDE4D1, D2, D3, D4 and D5). One or more PDE4D subtype variants are ubiquitously present in all mammalian cells. In CNS all five PDE4D subtype variants are expressed in varying ratios and their activity is regulated in tandem with GPCRs stimulation. Peripheral tissues also exhibit differential expression of PDE4D variants. PDE4D1/D2 mRNA levels rise in response to an increase in cAMP. Short term regulation of PDE4D variants involved PKA, MAP kinases and Erk2 phosphorylation that results in rapid change in their enzymatic activities. Other regulatory mechanism involved protein protein interactions with cytoskeletal scaffolding proteins.
Function:
Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes.
Subunit:
Homodimer for the long isoforms. Isoforms with truncated N-termini are monomeric. Isoform 3 is part of a ternary complex containing PRKAR2A, PRKAR2B and AKAP9. Interacts with PDE4DIP. Identified in a complex composed of RYR1, PDE4D, PKA, FKBP1A and protein phosphatase 1 (PP1). Isoform 5, isoform N3 and isoform 12 bind GNB2L1 via their unique N-terminus. Binds ARRB2.
Subcellular Location:
Cytoplasm. Membrane. Cytoplasm, cytoskeleton. Cytoplasm, cytoskeleton, centrosome. Note=Found in the soluble fraction, associated with membranes, and associated with the cytoskeleton and the centrosome.
Tissue Specificity:
Widespread; most abundant in skeletal muscle. Isoform 6 is detected in brain. Isoform 8 is detected in brain, placenta, lung and kidney. Isoform 7 is detected in heart and skeletal muscle.
Post-translational modifications:
Isoform 3 and isoform 7 are activated by phosphorylation (in vitro), but not isoform 6. Isoform N3 and isoform 12 are phosphorylated on Ser-49, Ser-51, Ser-55 and Ser-59.
Sumoylation of long isoforms by PIAS4 augments their activation by PKA phosphorylation and represses their inhibition by ERK phosphorylation.
DISEASE:
Note=Genetic variations in PDE4D might be associated with susceptibility to stroke. PubMed:17006457 states that association with stroke has to be considered with caution.
Similarity:
Belongs to the cyclic nucleotide phosphodiesterase family. PDE4 subfamily.
SWISS:
Q08499
Gene ID:
5144
Database links:
Entrez Gene: 5144 Human
Entrez Gene: 238871 Mouse
Entrez Gene: 24627 Rat
Omim: 600129 Human
SwissProt: Q08499 Human
SwissProt: P14270 Rat
Unigene: 117545 Human
Unigene: 95959 Rat
经研究发现磷酸二酯酶(PDE4D）基因可使缺血性卒中的危险性增高,使人患动脉粥样硬化及中风的风险性增高,有可能是通过影响动脉内平滑肌细胞的增生和扩散相关。目前，ＰＤＥ４Ｄ基因的变化机理并不是完全清楚，有待进一步研究
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Sample:Brain(Mouse) Lysate at 30 ug
Primary: Anti-PDE4D (SL1325R) at 1/300 dilution
Secondary: IRDye800CW Goat Anti-Mouse IgG at 1/20000 dilution
Predicted band size: 90 kD
Observed band size: 100 kD
Sample:Brain(Mouse) Lysate at 30 ug
Primary: Anti-PDE4D (SL1325R) at 1/300 dilution
Secondary: IRDye800CW Goat Anti-Mouse IgG at 1/20000 dilution
Predicted band size: 90 kD
Observed band size: 90kD
Sample:
Cerebrum (Mouse) Lysate at 40 ug
Primary: Anti- PDE4D (SL1325R) at 1/1000 dilution
Secondary: IRDye800CW Goat Anti-Rabbit IgG at 1/20000 dilution
Predicted band size: 90kD
Observed band size: 90 kD
Blank control: RSC96(blue), the cells were fixed with 2% paraformaldehyde (10 min) and then permeabilized with ice-cold 90% methanol for 30 min on ice..
Isotype Control Antibody: Rabbit IgG(orange) ;
Secondary Antibody: Goat anti-rabbit IgG-FITC(white blue),
Dilution: 1:200 in 1 X PBS containing 0.5% BSA ;
Primary Antibody Dilution: 1μg in 100 μgL 1X PBS containing 0.5% BSA(green).
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