unique C-terminal region of PDE4A7 was unable to support an active catalytic unit, whereas its unique N-terminal region can
exclusively localized to the P1 particulate fraction in cells
15
-
4608
126
860
widely expressed
2017
27993970
PDE4A11, isoform 2
unique, 81 amino acid N-terminal region
long isoform possessing UCR1 and UCR2 regulatory domains
interact with beta-arrestin, and weakly with LYN
activated by PKA phosphorylation and may contribute to compartmentalized cAMP signaling in cells in which it is expressed
cytoplasmic, ruffle membrane
-
-
2707
-
864
. could be detected in discrete regions of brain, including the cerebellum, spinal cord and cerebral cortex
. localized predominantly in the cytosol, but also associated with membrane fractions
. in normal pituitary
. mRNA was found to be expressed predominantly in skeletal muscle and brain
2017
27993970
PDE4A8
a novel N-terminal region of 85 amino acids that differs from those of the related 'long' PDE4A4, PDE4A10 and PDE4A11 isoforms
may have a specific function in regulating cAMP levels in human skeletal muscle and brain
may downregulate cyclic AMP signaling at the cell membrane and/or in the extracellular space at the time of granule release
regulating the cellular concentrations of cyclic nucleotides and thereby playing a role in signal transduction
regulating the viability of medulloblastoma cells (Schmidt 2010)
widely expressed in brain tumors and promoting their growth and that inihibition with Rolipram overcomes tumor resistance and mediates tumor regression (Goldhoff 2008)
upregulation of PDE4A expression during cholestatic liver injury plays a potential pathogenic role in the development of inflammation, injury, and fibrosis
AKAP1-PRKACA-PDE4A distribution and integrity have a key role in cellular survival
CELLULAR PROCESS
PHYSIOLOGICAL PROCESS
PATHWAY
metabolism
purine/pyrimidine
signaling
signal transduction
cAMP degradation
a component
INTERACTION
DNA
RNA
small molecule
protein
upregulation of NOX4 leads to an upregulation of PDE4A, PDE4B, and PDE4D and increased hydrolysis of cAMP which in turn augments cell replication and angiogenesis
DISC1 regulates cyclic adenosine monophosphate (cAMP) signaling via interactions with PDE4
PDE4A inhibition regulates VCAM1 through a novel RAPGEF3-dependent mechanism, which involves regulatory epigenetic components and reduces neointima formation following vascular injury
PDE4A long isoforms can be phosphorylated by MAPKAPK2, which attenuates activation of such enzymes through their phosphorylation by protein kinase A
interaction with over-expressed AIP does not seem to affect PDE2A function, but the reported effect on PDE4A is, in contrast, reduced enzymatic activity
cell & other
REGULATION
inhibited by
rolipram
Other
cleaved by caspase 3
ASSOCIATED DISORDERS
corresponding disease(s)
Other morbid association(s)
Type
Gene Modification
Chromosome rearrangement
Protein expression
Protein Function
constitutional
 
 
--low
 
in the striato-thalamo-cortical circuit, is associated with deficits of spatial working memory in patients with Parkinson disease
Susceptibility
Variant & Polymorphism
Candidate gene
Marker
Therapy target
inhibition of PDE4A inhibition diminish proliferation of lung fibroblasts and therefore could be useful in the therapy of pathological remodeling in lung diseases (Selige 2010)
is reduced in cerebellar of patients with bipolar disorder and provides potential potential new therapeutic avenues for treatment of this disorder (Fatemi 2008)