PDE4 inhibition together with transforming growth factor-beta1 results in augmented PGE2 production together with increased expression of COX mRNA and protein. inhibitors may attenuate fibroblast activities that can lead to fibrosis, PDE4 inhibitors may be particularly effective in the presence of transforming growth factor-beta1-induced fibroblast stimulation
a pdeHDELTA/pdeLDELTA mutant shows reduced conidiation, exhibits dramatically increased cAMP levels relative to the wild-type, and is completely defective in virulence
deletion of cpdA results in the accumulation of intracellular cAMP and altered regulation of Pseudomonas aeruginosa virulence traits. The cpdA mutant has a cAMP-independent small-colony, slow-growth phenotype
effects of acute hypoxia on cAMP accumulation induced by PDE inhibitors in oxygen-specific chemosensors, the carotid bodies and in non-chemosensitive CB-related structures: carotid arteries and superior cervical ganglia, overview. Acute hypoxia enhances the effects of IBMX and PDE4 inhibitors on cAMP accumulation in carotid arteries and bodies, while in superior cervical ganglia In SCG, acute hypoxia reduces cAMP accumulation induced by all the four PDE inhibitors
loss of PdeH leads to increased accumulation of intracellular cAMP during vegetative and infectious growth. Furthermore, the pdeHD shows 2-3fold enhanced conidiation, precocious appressorial development, loss of surface dependency during pathogenesis, and highly reduced in planta growth and host colonization. A pdeHDELTA/pdeLDELTA mutant shows reduced conidiation, exhibits dramatically increased cAMP levels relative to the wild-type, and is completely defective in virulence
PDE8B KO mice have elevated levels of urinary corticosterone in both basal and stressed conditions compared with their littermate wild-type controls. PDE8B KO mice exhibit adrenal hypersensitivity toward adrenocorticotropin. PDE8B gene ablation increases mRNA expressions of StAR protein and MC2R
cyclic AMP-dependent pathways mediate the communication between external stimuli and the intracellular signaling machinery, thereby influencing important aspects of cellular growth, morphogenesis and differentiation. Crucial to proper function and robustness of these signaling cascades is the strict regulation and maintenance of intracellular levels of cAMP through a fine balance between biosynthesis, by adenylate cyclases, and hydrolysis, by cAMP phosphodiesterases
PKA, EPAC1, and PDE4D differentially regulate humanarterial endothelial cell vascular endothelial cadherin-based structures, overview. Protein-protein interactions between EPAC1 and PDE4D serve to foster their integration into vascular endothelial cadherin-based complexes and allow robust local regulation of EPAC1-based stabilization of vascular endothelial cadherin-based adhesions
a transmembrane-adenylyl-cyclase-cAMP-protein kinase A cascade modulated by isoform PDE1C is critical in regulating platelet-derived growth factor -receptor-beta degradation
a transmembrane-adenylyl-cyclase-cAMP-protein kinase A cascade modulated by isoform PDE1C is critical in regulating platelet-derived growth factor -receptor-beta degradation
a transmembrane-adenylyl-cyclase-cAMP-protein kinase A cascade modulated by isoform PDE1C is critical in regulating platelet-derived growth factor -receptor-beta degradation
CpdA is required for cAMP homeostasis and virulence factor regulation, CpdA affects vfr expression and Vfr protein levels and production of virulence factors ExoS, ToxA, and protease IV
cAMP-specific PDE 4 isoforms underpin compartmentalized cAMP signalling in mammalian cells through targeting to specific signalling complexes. Phosphorylation of PDE4A5 by MK2 confers the amplification of intracellular cAMP accumulation in response to adenylate cyclase activation by attenuating a major desensitization system to cAMP. Long PDE4 isoforms thus provide a novel node for cross-talk between the cAMP and p38 MAPK signalling systems at the level of MK2
CpdA possesses 3',5'-cAMP phosphodiesterase activity in vitro and that it utilizes an iron-dependent catalytic mechanism. The cAMP-dependent transcription factor Vfr directly regulates cpdA expression in response to intracellular cAMP accumulation, thus providing a feedback mechanism for controlling cAMP levels and fine-tuning virulence factor expression. CpdA affects vfr expression and Vfr protein levels. CpdA affects production of virulence factors ExoS, ToxA, and protease IV
importance of PDE8s in cAMP regulation of steroid production. PDE8A plays an important role in regulating a pool of cAMP that promotes testicular steroidogenesis. PDE8B regulates adrenocorticotropin-stimulated AZF steroidogenesis by both short- and long-term mechanisms
in cardiac myocytes coupling of PDE4 members to the beta2 adrenergic receptor regulates several aspects of beta2 adrenergic signaling. Inhibition of PDE4 increases cAMP in response to activation of beta2 adrenergic receptors, but has no effect on beta1 adrenergic signaling, demonstrating the selectivity of PDE association. Recruitment of PDE4 to the beta2 adrenergic receptor allows PDE4 to act locally and hydrolyze cAMP produced in response to activation of this receptor, modulating its downstream effects. PDE4 activation is regulated via phosphorylation by PKA in the UCR or phosphorylation by ERK in the C-terminus, depending on the individual isoform. The regulated release of ATP from erythrocytes occurs via a defined signaling pathway and requires increases in cAMP. It is well recognized that cAMP is a critical second messenger in diverse signaling pathways. In all cells increases in cAMP are localized and regulated by the activity of phosphodiesterases, PDEs. The subcellular localization of PDEs is recognized to be a key mechanism for compartmentalization of cyclic nucleotide signaling. PDEs within these cells regulate the compartmentalization of cAMP signaling allowing for specific cell responses. The subcellular location of PDEs is critical for coupling these enzymes to specific signal transduction pathways, which permit specific PDEs to regulate local increases in cAMP produced by activation of ligand specific receptor
PDEH is necessary for proper aerial hyphal growth. PdeH-dependent biphasic regulation of cAMP levels during early and late stages of appressorial development. PdeH-mediated sustainance and dynamic regulation of cAMP signaling during Magnaporthe oryzae development is crucial for successful establishment and spread of the blast disease in rice. The PdeH activity is a key regulator of asexual and pathogenic development in Magnaporthe oryzae
the autocrine production of cAMP and extracellular cAMP-specific phosphodiesterase is an important constituent of the mechanism controlling the motile behavior of the plasmodium
the PDE4-catalyzed hydrolysis of cAMP consists of two reaction stages: cAMP hydrolysis and bridging hydroxide ion regeneration. The stage 1 includes the binding of cAMP in the active site, nucleophilic attack of the bridging hydroxide ion on the phosphorus atom of cAMP, cleavage of O3'-P phosphoesteric bond of cAMP, protonation of the departing O3' atom, and dissociation of hydrolysis product, AMP. The stage 2 includes the binding of solvent water molecules with the metal ions in the active site and regeneration of the bridging hydroxide ion. The dissociation of the hydrolysis product is found to be rate-determining for the enzymatic reaction process
constitutive signaling of the overexpressed HA-tagged 5-hydroxytryptamine4(b) receptor in HEK293 cells is regulated predominantly by cAMP-specific phosphodiesterase PDE4,with a secondary role for dual specific phosphodiesterase PDE3 that is unmasked in the presence of PDE4 inhibition. Overexpressed PDE4D3 and PDE3A1, and to a smaller extent PDE4D5 co-immunoprecipitate constitutively with the 5-hydroxytryptamine4(b) receptor. Phosphodiesterase activity measurements in immunoprecipitates of the 5-hydroxytryptamine4(b) receptor confirm the association of PDE4D3 with the receptor and provide evidence that the activity of this phophodiesterase may be increased upon receptor stimulation with 5-hydroxytryptamine
isoform PDE4B is involved in beta-adrenergic signaling in the heart. Genetic ablation of PDE4B disrupts beta-adrenergic signaling-induced cAMP transients at the sarcolemma but not in the bulk cytosol of cardiomyocytes. PDE4B regulates beta1-adrenergic signaling-, but not beta2-adrenergic signaling- or PGE2-induced responses. PDE4B shows selective effects on protein kinase A-mediated phosphorylation patterns. PDE4B limits the proein kinase A-mediated phosphorylation of key players in excitation-contraction coupling that reside in the sarcolemmal compartment, including L-type Ca2+ channels and ryanodine receptors, but not phosphorylation of distal cytosolic proteins. beta1-Adrenergic signaling- but not beta2-adrenergic signaling-ligation induced protein kinase A-dependent activation of PDE4B and interruption of this negative feedback with protein kinase A inhibitors increase sarcolemmal cAMP
mutation in cAMP-specific phosphodiesterase RegA in cells lacking either G protein Galpha2 or Galpha4 subunits has no major effects on developmental morphology but enriches the distribution of the Galpha mutant cells to the prespore/prestalk border in chimeric aggregates. The loss of RegA function has no effect on Galpha4-mediated folate chemotaxis. The RegA gene disruption in cells lacking Galpha4 results in a substantial rescue and acceleration of spore production. This rescue in sporulation requires cell autonomous signaling. Intercellular signals from strains lacking RegA increase the expression of the prestalk gene ecmB and accelerate the vacuolization of stalk cells. Intercellular signaling from the strain lacking both Galpha4 and RegA do not induce ecmA gene expression indicating cell-type specificity in the promotion of prestalk cell development. RegA gene disruption in a Galpha4 overexpression strain does not result in precocious sporulation or stalk cell development
phosphodiesterase 4B mediates Streptococcus pneumoniae-induced mucin gene MUC5AC up-regulation by inhibiting the expression of a negative regulator MKP-1, which in turn leads to enhanced MAPK ERK activation and subsequent up-regulation of MUC5AC. PDE4B inhibits MKP-1 expression in a cAMP-PKA-dependent manner. PDE4-specific inhibitor rolipram inhibits Streptomyces pneumoniae-induced MUC5AC up-regulation both in vitro and in vivo. PDE4B plays a critical role in MUC5AC induction. Topical and post-infection administration of rolipram into the middle ear potently inhibits Streptomyces pneumoniae-induced MUC5AC up-regulation
cAMP-phosphodiesterase 1C plays a role in regulating growth factor receptor stability, vascular smooth muscle cell growth, migration, and neointimal hyperplasia
cAMP-phosphodiesterase 1C plays a role in regulating growth factor receptor stability, vascular smooth muscle cell growth, migration, and neointimal hyperplasia
cAMP-phosphodiesterase 1C plays a role in regulating growth factor receptor stability, vascular smooth muscle cell growth, migration, and neointimal hyperplasia