Affinage

PDE3A

cGMP-inhibited 3',5'-cyclic phosphodiesterase 3A · UniProt Q14432

Length
1141 aa
Mass
125.0 kDa
Annotated
2026-04-29
70 papers in source corpus 27 papers cited in narrative 27 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PDE3A is a dual-specificity cyclic nucleotide phosphodiesterase that hydrolyzes cAMP and cGMP, with cGMP also acting as a competitive inhibitor, and serves as a critical regulator of cAMP compartmentalization in cardiovascular, reproductive, and hematopoietic cells (PMID:10828019, PMID:8695850). Three N-terminal isoforms (PDE3A1/136 kDa, PDE3A2/118 kDa, PDE3A3/94 kDa), generated by alternative translation initiation from a single gene, differ in membrane-association domains and phosphorylation sites, conferring distinct subcellular localizations and signalosome partnerships: PKA phosphorylation of PDE3A1 at Ser-292/293 drives its assembly into a SERCA2/AKAP18 complex at the sarcoplasmic reticulum to control cardiac contractility, PKB/Akt phosphorylation at Ser-290–292 activates PDE3A in oocytes to lower cAMP and permit meiotic resumption, and PKC phosphorylation in platelets promotes 14-3-3 binding and cAMP suppression (PMID:12154085, PMID:25593322, PMID:17124499, PMID:19261611). In vascular smooth muscle cells, PDE3A deletion elevates PKA activity, which inhibits Raf-1/ERK signaling and induces p21/p53-dependent G0/G1 arrest, suppressing proliferation (PMID:21632535). Gain-of-function PDE3A mutations cause autosomal dominant hypertension with brachydactyly type E, and independently of catalytic activity, small-molecule molecular glues induce PDE3A to form a heterotetramer with SLFN12, activating SLFN12 RNase/translational shutdown and triggering cancer cell apoptosis (PMID:25961942, PMID:34272366, PMID:34707099).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 1992 Medium

    Establishing that PDE3A is hormonally regulated by phosphorylation set the stage for understanding how catecholamines and insulin tune cAMP hydrolysis in intact cells.

    Evidence 32P metabolic labeling and immunoprecipitation in 3T3-L1 adipocytes after beta-agonist or insulin stimulation

    PMID:1314573

    Open questions at the time
    • Kinase identity not determined
    • Phosphorylation sites not mapped
    • Functional consequence on PDE activity not directly measured
  2. 1996 High

    Defining the catalytic domain boundaries (residues 679–1141) and identifying essential metal-coordinating histidine/glutamate residues resolved how PDE3A achieves dual cAMP/cGMP hydrolysis and how cGMP acts as a competitive inhibitor.

    Evidence Systematic deletion mutagenesis in PDE-deficient yeast and site-directed mutagenesis with kinetic analysis of recombinant enzyme

    PMID:10828019 PMID:8695850 PMID:9826434

    Open questions at the time
    • No crystal structure of PDE3A catalytic domain alone at this stage
    • Precise mechanism of cGMP competitive inhibition at atomic resolution unresolved
  3. 2001 High

    Discovery that the PDE3A N-terminal region encodes membrane-association determinants and that alternative pre-translational mechanisms generate tissue-specific isoforms (PDE3A1 vs PDE3A2) explained how a single gene produces proteins with distinct subcellular distributions in heart versus vasculature.

    Evidence Subcellular fractionation of N-terminal truncation mutants, 5'-RACE, and isoform-specific antibodies across rat tissues and VSMCs

    PMID:11115397 PMID:11420239 PMID:9884079

    Open questions at the time
    • Mechanism of alternative translation initiation not fully characterized
    • Functional non-redundancy of isoforms not yet demonstrated
  4. 2002 High

    Identification of three cardiac PDE3A isoforms (PDE3A1/136, PDE3A2/118, PDE3A3/94 kDa) from two mRNAs, each with unique N-terminal PKA/PKB sites, established the molecular basis for isoform-specific regulation in the heart.

    Evidence Isoform-specific antibodies, in vitro transcription/translation, RT-PCR in cardiac myocytes

    PMID:12154085

    Open questions at the time
    • In vivo functional distinction between isoforms in intact heart not yet shown
  5. 2006 High

    Demonstrating that PKB/Akt phosphorylates PDE3A at Ser-290–292 to activate cAMP hydrolysis and trigger meiotic resumption revealed PDE3A as the critical effector downstream of insulin/PI3K signaling in oocyte maturation.

    Evidence Cell-free kinase assay, Ser-to-Ala mutagenesis, microinjection of myr-Akt, pde3a−/− oocyte rescue in Xenopus and mouse

    PMID:17124499

    Open questions at the time
    • Whether additional kinases co-regulate PDE3A in oocytes not excluded
    • Structural basis of phosphorylation-induced activation unknown
  6. 2009 High

    Mapping five PKC-dependent phosphorylation sites (Ser-312, -428, -438, -465, -492) on platelet PDE3A and showing that these drive 14-3-3 binding revealed a distinct kinase-specific regulatory module controlling cAMP in hemostasis.

    Evidence Mass spectrometry phosphosite identification, selective kinase inhibitors, co-IP with 14-3-3 in thrombin-stimulated platelets

    PMID:19261611

    Open questions at the time
    • Functional consequence of individual phosphosites on platelet aggregation not dissected
    • Identity of specific 14-3-3 isoforms involved not defined
  7. 2010 High

    Showing that PDE3A−/− oocytes arrest at G2/M because elevated PKA inactivates Plk1 and Cdc2, and that PDE3A co-immunoprecipitates with Plk1, positioned PDE3A within the meiotic cell-cycle kinase cascade.

    Evidence PDE3A knockout mouse oocytes, in vitro PKA phosphorylation of Plk1, co-IP, PKA inhibitor rescue

    PMID:21099356

    Open questions at the time
    • Direct PKA phosphosite on Plk1 that mediates inhibition not mapped in vivo
    • Whether PDE3A-Plk1 interaction is direct or scaffold-mediated unknown
  8. 2010 High

    Demonstration that PDE3A interacts with CFTR at the plasma membrane and that actin cytoskeleton integrity is required for this compartmentalized cAMP signaling revealed PDE3A as a regulator of chloride channel function.

    Evidence Reciprocal co-IP, CFTR electrophysiology, actin disruption in airway epithelial cells

    PMID:20089840

    Open questions at the time
    • Whether PDE3A directly binds CFTR or via an adaptor not resolved
    • Physiological impact on mucociliary clearance not tested in vivo
  9. 2011 High

    PDE3A deletion in VSMCs established that PDE3A sustains proliferative signaling through two parallel cAMP-PKA-suppressive arms: enabling Raf-1/ERK activation and preventing p21/p53-mediated G0/G1 arrest.

    Evidence PDE3A knockout mouse VSMCs, adenoviral CREB overexpression, p53 siRNA rescue, ERK/Raf-1 phosphorylation assays

    PMID:21632535

    Open questions at the time
    • Contribution of PDE3A versus PDE3B to in vivo vascular remodeling not separated
    • Relevance to human atherosclerotic VSMCs not confirmed
  10. 2013 High

    Revealing that PKA selectively phosphorylates PDE3A1 at Ser-312 (promoting 14-3-3 binding without increasing activity) while PKC selectively phosphorylates PDE3A2 at Ser-428 (stimulating activity) demonstrated isoform-specific regulatory logic within the same cell type.

    Evidence FLAG-tagged isoform expression in HEK293, phospho-specific detection, gel filtration, validated in human myocardium

    PMID:24248367

    Open questions at the time
    • Distinct interactomes of PDE3A1 vs PDE3A2 identified by 2D-gel but individual partners not validated
    • Functional cardiac phenotype of isoform-selective disruption not tested
  11. 2015 High

    PKA phosphorylation of PDE3A1 at Ser-292/293 was shown to drive its incorporation into a SERCA2/AKAP18 signalosome at the sarcoplasmic reticulum, directly linking PDE3A1 to regulation of PLB phosphorylation and cardiac contractility.

    Evidence Co-IP, gel filtration, Ser-to-Ala mutagenesis, recombinant protein reconstitution in human SR fractions

    PMID:25593322

    Open questions at the time
    • In vivo cardiac functional consequence of disrupting PDE3A1-AKAP18 interaction not demonstrated
    • Stoichiometry of the signalosome not determined
  12. 2015 High

    Identification of gain-of-function PDE3A mutations as the cause of autosomal dominant hypertension with brachydactyly type E established PDE3A as a disease gene and connected enhanced cAMP hydrolysis to vascular and skeletal pathology.

    Evidence In vitro cAMP hydrolysis assays on MSC-derived VSMCs/chondrocytes from mutation carriers, phospho-VASP and PTHrP measurements

    PMID:25961942

    Open questions at the time
    • Precise structural mechanism by which mutations enhance phosphorylation-dependent activation not resolved
    • Contribution of vascular versus skeletal phenotype to hypertension not dissected
  13. 2015 High

    Discovery that small-molecule DNMDP induces a neomorphic PDE3A–SLFN12 protein-protein interaction essential for selective cancer cell killing opened a catalysis-independent, molecular-glue function for PDE3A.

    Evidence Chemogenomic screening across 766 cancer cell lines, co-IP, siRNA resistance studies

    PMID:26656089

    Open questions at the time
    • Mechanism of cell death downstream of PDE3A-SLFN12 complex not yet defined
    • Structural basis of glue-induced interaction unknown at this point
  14. 2021 High

    Cryo-EM and crystal structures of the PDE3A–SLFN12 heterotetramer revealed that molecular glues bind the PDE3A catalytic pocket and create a hydrophobic interface that recruits a SLFN12 C-terminal helix, activating SLFN12 RNase activity to block translation and induce apoptosis.

    Evidence Cryo-EM structures with DNMDP/anagrelide/nauclefine, mutagenesis of interface residues, in vitro RNase assay

    PMID:34272366 PMID:34707099

    Open questions at the time
    • In vivo tRNA substrate specificity of activated SLFN12 not fully characterized
    • Determinants of cancer-cell selectivity beyond PDE3A-SLFN12 coexpression not defined
  15. 2022 High

    Showing that PDE3A-SLFN12 complex formation triggers SLFN12 dephosphorylation at Ser-368/Ser-573 and that this dephosphorylation is required for rRNA cleavage and cell death added a phosphorylation-dependent gating step to the molecular-glue killing mechanism.

    Evidence Co-IP, phosphosite-mimetic/alanine mutagenesis of SLFN12, RNase activity assay, cell viability readouts

    PMID:35104454

    Open questions at the time
    • Phosphatase responsible for SLFN12 dephosphorylation not identified
    • Whether other Schlafen family members can substitute for SLFN12 not tested

Open questions

Synthesis pass · forward-looking unresolved questions
  • Major open questions include: the structural basis of phosphorylation-induced PDE3A activation, the atomic-resolution structure of PDE3A catalytic domain alone, the in vivo cardiac phenotype of isoform-selective PDE3A disruption, the phosphatase acting on SLFN12 in the molecular-glue pathway, and the determinants beyond coexpression that confer cancer-cell selectivity to velcrin compounds.
  • No high-resolution structure of PDE3A catalytic domain alone
  • In vivo isoform-selective genetic models lacking
  • Phosphatase for SLFN12 dephosphorylation unidentified

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016787 hydrolase activity 4 GO:0009975 cyclase activity 3
Localization
GO:0005886 plasma membrane 3 GO:0005829 cytosol 2 GO:0043226 organelle 2
Pathway
R-HSA-162582 Signal Transduction 6 R-HSA-5357801 Programmed Cell Death 4 R-HSA-1640170 Cell Cycle 3 R-HSA-1474165 Reproduction 2 R-HSA-397014 Muscle contraction 1
Partners
AKAP18ATP2A2CFTRPLK1PLNPPP2CASLFN12YWHAZ
Complex memberships
PDE3A-SLFN12 heterotetramerSERCA2/AKAP18/PDE3A1 signalosome

Evidence

Reading pass · 27 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2002 Three PDE3A isoforms (PDE3A-136, PDE3A-118, PDE3A-94) exist in cardiac myocytes, translated from two mRNAs derived from the PDE3A1 gene; they differ in N-terminal sequences containing membrane-association domains and phosphorylation/activation sites for PKA and PKB, determining their distinct subcellular localizations. Western blotting with isoform-specific antibodies, in vitro transcription/translation, RT-PCR The Journal of biological chemistry High 12154085
2006 PKB/Akt phosphorylates PDE3A at serines 290-292 in mouse oocytes, increasing cAMP-hydrolytic activity and promoting meiotic maturation; mutation of these serines to alanine greatly diminishes insulin-dependent maturation in Xenopus and mouse oocytes. Cell-free kinase assay with recombinant PDE3A and PKB/Akt, site-directed mutagenesis, microinjection of myr-Akt into oocytes, pde3a(-/-) rescue experiments The EMBO journal High 17124499
2015 Phosphorylation of human PDE3A1 by PKA at Ser-292/Ser-293 (unique to PDE3A1 N-terminal extension) promotes incorporation of PDE3A1 into a SERCA2/AKAP18 signalosome in the sarcoplasmic reticulum, where it regulates PLB phosphorylation and SERCA2 activity controlling cardiac contractility. Co-immunoprecipitation, gel filtration chromatography, recombinant protein phosphorylation assay, N-terminal deletion mutants, Ser-to-Ala substitution mutagenesis, immunohistochemistry The Journal of biological chemistry High 25593322
2015 Gain-of-function missense mutations in PDE3A increase PKA-mediated phosphorylation of PDE3A, resulting in increased cAMP-hydrolytic activity, enhanced VSMC and chondrocyte proliferation, diminished phospho-VASP levels, and dysregulated PTHrP, causing autosomal dominant hypertension with brachydactyly. In vitro cAMP hydrolysis assays on MSC-derived VSMCs and chondrocytes, analysis of phosphorylation state, VASP and PTHrP measurements Nature genetics High 25961942
2015 DNMDP binding to PDE3A promotes a neomorphic protein-protein interaction between PDE3A and Schlafen 12 (SLFN12), and coexpression of both proteins is required for DNMDP-induced cancer cell death; PDE3A depletion confers DNMDP resistance. Phenotypic compound library screening across 766 cancer cell lines, target deconvolution by predictive chemogenomics, co-immunoprecipitation, siRNA knockdown Nature chemical biology High 26656089
2021 PDE3A and SLFN12 form a heterotetramer stabilized by DNMDP; interactions between the C-terminal alpha helix of SLFN12 and residues near the PDE3A active site are required for complex formation; PDE3A binding increases SLFN12 RNase activity, and SLFN12 RNase activity is required for DNMDP-induced cell death. Crystal/cryo-EM structure of PDE3A-SLFN12 complex, mutagenesis of interface residues, in vitro RNase activity assay Nature communications High 34272366
2021 Cryo-EM structures of PDE3A-SLFN12 heterotetramer bound to anagrelide, nauclefine, or DNMDP reveal that molecular glue compounds bind the PDE3A catalytic domain pocket and create a modified interface that recruits the SLFN12 short helix (E552-I558) via hydrophobic interactions; SLFN12 activation blocks protein translation leading to apoptosis. High-resolution cryo-EM of complexes isolated from drug-treated HeLa cells, structure-based analog design Nature communications High 34707099
2009 Platelet agonists (e.g., thrombin via PAR-1) activate PKC to phosphorylate PDE3A on Ser-312, Ser-428, Ser-438, Ser-465, and Ser-492, increasing cAMP hydrolysis and promoting association of PDE3A with 14-3-3 proteins; PKC activation, but not PI3K/PKB, mTOR/p70S6K, or ERK/RSK, is required for this phosphorylation. Mass spectrometry phosphosite identification, pharmacological inhibition of kinase pathways, co-immunoprecipitation with 14-3-3 The Journal of biological chemistry High 19261611
2002 In gastric smooth muscle, PKA phosphorylates PDE3A (not PDE3B) and activates its cAMP-hydrolytic activity; cGMP inhibits PDE3 activity and augments cAMP levels; PKG does not regulate PDE3A phosphorylation. RT-PCR/Western blot for isoform identification, PKA/PKG-selective pharmacological tools (PKI, H-89, KT-5823), PDE activity assays, phosphorylation assays American journal of physiology. Cell physiology High 11832336
2011 PDE3A deletion in VSMCs suppresses mitogen-induced proliferation via two complementary pathways: (1) elevated PKA activity causes inhibitory phosphorylation of Raf-1 (Ser-259), reducing ERK activation; (2) PKA/CREB-mediated induction of p21 and p53 accumulation elevates MKP-1 and causes G0/G1 cell cycle arrest. PDE3A knockout mouse VSMCs, adenoviral CREB overexpression, siRNA knockdown of p53, ERK/Raf-1 phosphorylation assays, cell cycle analysis The Journal of biological chemistry High 21632535
2013 PDE3A1 and PDE3A2 isoforms are phosphorylated at different sites by distinct kinases in cardiac myocytes: isoproterenol/PKA selectively phosphorylates PDE3A1 at S312 (14-3-3 binding site), while PMA/PKC selectively phosphorylates PDE3A2 at S428; phosphorylation at S428 stimulates PDE3A2 activity but S312 phosphorylation does not affect PDE3A1 activity; the two isoforms have distinct protein interactomes. FLAG-tagged isoform expression in HEK293 cells, phospho-specific detection, gel filtration chromatography, 2D electrophoresis of co-immunoprecipitated proteins, human myocardium validation Proceedings of the National Academy of Sciences of the United States of America High 24248367
2010 PDE3A physically and functionally interacts with CFTR at the plasma membrane; PDE3A inhibition generates compartmentalized cAMP that further clusters PDE3A and CFTR into microdomains; actin cytoskeleton disruption reduces PDE3A-CFTR interaction and abolishes compartmentalized cAMP signaling and CFTR channel potentiation. Co-immunoprecipitation, pharmacological PDE3A inhibition, actin disruption, CFTR channel electrophysiology, gland secretion assay Molecular biology of the cell High 20089840
2000 Conserved histidine and glutamate residues in the two HXXXH(X)25E metal-binding motifs of PDE3A are critical for catalysis and substrate/inhibitor binding: H752, H756, E825 mutations abolish or greatly reduce catalytic activity; H836A increases Ki for cGMP 177-fold; E866A increases Km for cAMP 11-fold and Ki for cGMP 27-fold; E971A increases Km 5-fold. Site-directed mutagenesis, expression in baculovirus/Sf9 system, kinetic analysis (kcat, Km, Ki) Blood High 10828019
1998 Site-directed mutagenesis of platelet PDE3A identified H840 as essential for catalysis (likely coordinates Mn2+) and H869 as important for cGMP inhibitor binding (H869A increases Km for cAMP and IC50 for cGMP fourfold each); C816 in the 44-aa PDE3-unique insert is essential for proper folding. Site-directed mutagenesis, expression in PDE-deficient yeast Saccharomyces cerevisiae, kinetic analysis Archives of biochemistry and biophysics High 9826434
1996 The PDE3A catalytic domain is localized to amino acid residues 679-1141; deletion constructs PDE3Adelta1 (aa 665-1141) and PDE3Adelta2 (aa 679-1141) retain catalytic activity, while PDE3Adelta3 (aa 686-1141) and PDE3Adelta4 (aa 700-1141) do not. Deletion mutagenesis, expression in PDE-deficient yeast, PDE activity assays, Western blotting Blood High 8695850
2001 Mouse oocyte PDE3A is recovered predominantly in the soluble fraction when N-terminally truncated (Delta346aa or Delta608aa), whereas full-length recombinant PDE3A is in the particulate fraction; the N-terminal region contains the membrane-association determinants. Subcellular fractionation of Leydig cell-expressed truncation mutants, pharmacological profiling vs. oocyte PDE activity Biology of reproduction High 11420239
2001 A vascular smooth muscle cell PDE3A isoform (PDE3A2/~118 kDa) is generated from the same gene as cardiac PDE3A1 via a pre-translational mechanism that removes the first 145 N-terminal amino acids of PDE3A1, including one membrane-association domain. cDNA cloning from aortic myocytes, 5'-RACE, RT-PCR, ribonuclease protection assay, Western blotting with region-specific antibodies, Sf9 expression The Biochemical journal High 11115397
2010 In PDE3A(-/-) oocytes, elevated PKA activity inactivates both Cdc2 and Plk1, inhibits histone H3-S10 phosphorylation and Cdc25B dephosphorylation, causing G2/M arrest; PKAc fails to translocate to the nucleus; Plk1 is reactivated by PKA inhibitor; PDE3A co-immunoprecipitates with Plk1 and PKAc can phosphorylate and inhibit Plk1 in vitro. PDE3A knockout mouse oocytes, in vitro PKA phosphorylation of recombinant Plk1, co-immunoprecipitation, PKA inhibitor (Rp-cAMPS) rescue, subcellular localization imaging Cell cycle (Georgetown, Tex.) High 21099356
1998 In rat tissues and VSMCs, PDE3A is expressed as a ~120 kDa protein found exclusively in the cytosolic fraction, whereas PDE3B (~135 kDa) is found only in the particulate fraction; prolonged elevation of cAMP increases PDE3A and PDE3B expression and shifts PDE3 activity to particulate fractions. Subcellular fractionation, immunoblotting with isoform-selective antisera, RT-PCR, cAMP-elevating agent treatment British journal of pharmacology High 9884079
2015 Chemical proteomics using an IBMX-based affinity resin in HeLa cells identified the PDE3A interactome, including 14-3-3 proteins and a PP2A complex (regulatory, scaffold, and catalytic subunits) as endogenous PDE3A-associated proteins. Chemical proteomics (IBMX-affinity resin + selective competitor PDE inhibitors), mass spectrometry identification of co-purified proteins Molecular bioSystems Medium 26205238
2016 PDE3A hydrolyzes cUMP with low affinity (Km ~143 μM) and high velocity (Vmax ~42 μmol/min/mg), compared to cAMP (Km ~0.7 μM, Vmax ~1.2 μmol/min/mg); the PDE3 inhibitor milrinone inhibits cUMP hydrolysis by PDE3A with Ki = 57 nM. In vitro enzyme kinetics with HPLC-MS/MS detection of UMP and AMP products, milrinone inhibition assay Naunyn-Schmiedeberg's archives of pharmacology Medium 27975297
2022 Cytotoxic PDE3A modulators act as molecular glues inducing PDE3A-SLFN12 association; the PDE3A-SLFN12 interaction stabilizes cytoplasmic SLFN12 and induces SLFN12 dephosphorylation at Ser-368 and Ser-573; this dephosphorylation is required for cell death and promotes rRNA RNase activity of SLFN12. Co-immunoprecipitation, mutational analysis of SLFN12 phosphosites, RNase activity assay, cell viability with phospho-mimetic/alanine mutants Cell chemical biology High 35104454
2019 ATF3 transcription factor binds a 29-nt insertion polymorphism in the PDE3A promoter and represses cAMP-dependent PDE3A1 transcription; a nearby cAMP response element enhancer is blocked by the insertion, explaining differential PDE3A1 expression in response to PDE3 inhibitor treatment in heart failure patients. Luciferase reporter assay, mRNA RT-PCR in explanted human LV, PDE enzyme activity assay, promoter deletion analysis Journal of the American College of Cardiology Medium 30871701
2017 SFPQ (splicing factor proline and glutamine rich) binds upstream regulatory regions of PDE3A and activates its transcription; serum-induced PDE3A expression is dependent on SFPQ binding; PDE3A transcription initiates from multiple start sites within exon 1. 5'-RACE for transcription start site mapping, ChIP-seq for SFPQ binding sites, SFPQ overexpression and knockdown effects on PDE3A mRNA Bioscience reports Medium 28743736
2020 In human pulmonary artery smooth muscle cells, nitric oxide increases PDE3A protein expression and PDE3 activity via the sGC-cGMP pathway, leading to decreased cAMP and increased AMPK phosphorylation; siRNA knockdown of PDE3A blunts NO-induced AMPK activation. siRNA knockdown, Western blotting, cAMP assay, pharmacological sGC stimulator/inhibitor Physiological reports Medium 32914566
2019 miR-27a-3p and miR-222-3p directly reduce PDE3A protein expression in human cerebral microvascular endothelial cells (hCMEC/D3) when transfected as mimics. miRNA mimic transfection, Western blotting Molecular neurobiology Low 30603956
1992 The cGMP-inhibited PDE (PDE3A) in 3T3-L1 adipocyte particulate fractions is phosphorylated in response to beta-agonist or insulin in intact cells, indicating hormonal regulation of PDE3A phosphorylation state. 32P metabolic labeling, immunoprecipitation with anti-cGI PDE antibody Biochemical and biophysical research communications Medium 1314573

Source papers

Stage 0 corpus · 70 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2015 PDE3A mutations cause autosomal dominant hypertension with brachydactyly. Nature genetics 127 25961942
2002 Isoforms of cyclic nucleotide phosphodiesterase PDE3A in cardiac myocytes. The Journal of biological chemistry 107 12154085
2006 Protein kinase B/Akt phosphorylation of PDE3A and its role in mammalian oocyte maturation. The EMBO journal 101 17124499
1998 Expression of cyclic GMP-inhibited phosphodiesterases 3A and 3B (PDE3A and PDE3B) in rat tissues: differential subcellular localization and regulated expression by cyclic AMP. British journal of pharmacology 96 9884079
2015 Regulation of sarcoplasmic reticulum Ca2+ ATPase 2 (SERCA2) activity by phosphodiesterase 3A (PDE3A) in human myocardium: phosphorylation-dependent interaction of PDE3A1 with SERCA2. The Journal of biological chemistry 83 25593322
2015 Identification of cancer-cytotoxic modulators of PDE3A by predictive chemogenomics. Nature chemical biology 81 26656089
2009 Protein kinase C-mediated phosphorylation and activation of PDE3A regulate cAMP levels in human platelets. The Journal of biological chemistry 79 19261611
2015 Targeted disruption of PDE3B, but not PDE3A, protects murine heart from ischemia/reperfusion injury. Proceedings of the National Academy of Sciences of the United States of America 73 25877153
2021 Structure of PDE3A-SLFN12 complex reveals requirements for activation of SLFN12 RNase. Nature communications 70 34272366
2002 PKA-dependent activation of PDE3A and PDE4 and inhibition of adenylyl cyclase V/VI in smooth muscle. American journal of physiology. Cell physiology 69 11832336
2011 Phosphodiesterase 3A (PDE3A) deletion suppresses proliferation of cultured murine vascular smooth muscle cells (VSMCs) via inhibition of mitogen-activated protein kinase (MAPK) signaling and alterations in critical cell cycle regulatory proteins. The Journal of biological chemistry 65 21632535
2010 Compartmentalized cyclic adenosine 3',5'-monophosphate at the plasma membrane clusters PDE3A and cystic fibrosis transmembrane conductance regulator into microdomains. Molecular biology of the cell 63 20089840
2001 Cloning and characterization of the cyclic guanosine monophosphate-inhibited phosphodiesterase PDE3A expressed in mouse oocyte. Biology of reproduction 62 11420239
2013 GWAS replication study confirms the association of PDE3A-SLCO1C1 with anti-TNF therapy response in rheumatoid arthritis. Pharmacogenomics 59 23651021
2001 Identification of a novel isoform of the cyclic-nucleotide phosphodiesterase PDE3A expressed in vascular smooth-muscle myocytes. The Biochemical journal 42 11115397
1996 Human platelet cGI-PDE: expression in yeast and localization of the catalytic domain by deletion mutagenesis. Blood 40 8695850
2021 Structure of PDE3A-SLFN12 complex and structure-based design for a potent apoptosis inducer of tumor cells. Nature communications 38 34707099
2013 Selective regulation of cyclic nucleotide phosphodiesterase PDE3A isoforms. Proceedings of the National Academy of Sciences of the United States of America 33 24248367
2011 Role of PDE3A in regulation of cell cycle progression in mouse vascular smooth muscle cells and oocytes: implications in cardiovascular diseases and infertility. Current opinion in pharmacology 33 22051884
2019 miRNA-27a-3p and miRNA-222-3p as Novel Modulators of Phosphodiesterase 3a (PDE3A) in Cerebral Microvascular Endothelial Cells. Molecular neurobiology 31 30603956
2022 Multiple PDE3A modulators act as molecular glues promoting PDE3A-SLFN12 interaction and induce SLFN12 dephosphorylation and cell death. Cell chemical biology 25 35104454
2019 PDE3A inhibitor anagrelide activates death signaling pathway genes and synergizes with cell death-inducing cytokines to selectively inhibit cancer cell growth. American journal of cancer research 25 31598394
2019 Optimization of PDE3A Modulators for SLFN12-Dependent Cancer Cell Killing. ACS medicinal chemistry letters 25 31749907
2000 Conserved amino acids in metal-binding motifs of PDE3A are involved in substrate and inhibitor binding. Blood 25 10828019
1996 Molecular cloning and chromosomal assignment of the human homologue of the rat cGMP-inhibited phosphodiesterase 1 (PDE3A)--a gene involved in fat metabolism located at 11p 15.1. Genomics 25 8921398
2020 Di (2-ethylhexyl) phthalate impairs primordial follicle assembly by increasing PDE3A expression in oocytes. Environmental pollution (Barking, Essex : 1987) 24 33234378
2016 A PDE3A mutation in familial hypertension and brachydactyly syndrome. Journal of human genetics 24 27053290
2019 Phosphodiesterase type 3A (PDE3A), but not type 3B (PDE3B), contributes to the adverse cardiac remodeling induced by pressure overload. Journal of molecular and cellular cardiology 23 31051182
2019 A PDE3A Promoter Polymorphism Regulates cAMP-Induced Transcriptional Activity in Failing Human Myocardium. Journal of the American College of Cardiology 19 30871701
2020 Nitric oxide activates AMPK by modulating PDE3A in human pulmonary artery smooth muscle cells. Physiological reports 16 32914566
2017 PDE3A is hypermethylated in cisplatin resistant non-small cell lung cancer cells and is a modulator of chemotherapy response. European review for medical and pharmacological sciences 16 28678321
1998 Partial characterization of the active site human platelet cAMP phosphodiesterase, PDE3A, by site-directed mutagenesis. Archives of biochemistry and biophysics 16 9826434
2000 Cardiac type cGMP-inhibited phosphodiesterase (PDE3A) gene structure: similarity and difference to adipocyte type PDE3B gene. Biochemical and biophysical research communications 15 10679291
2010 Female infertility in PDE3A(-/-) mice: polo-like kinase 1 (Plk1) may be a target of protein kinase A (PKA) and involved in meiotic arrest of oocytes from PDE3A(-/-) mice. Cell cycle (Georgetown, Tex.) 14 21099356
1998 Downregulation of right ventricular phosphodiesterase PDE-3A mRNA and protein before the development of canine heart failure. Cell biochemistry and biophysics 14 9631239
2023 Mutations in Phosphodiesterase 3A (PDE3A) Cause Hypertension Without Cardiac Damage. Hypertension (Dallas, Tex. : 1979) 13 37035914
2023 ETV1 inhibition depressed M2 polarization of tumor-associated macrophage and cell process in gastrointestinal stromal tumor via down-regulating PDE3A. Journal of clinical biochemistry and nutrition 12 36936869
2019 Electroacupuncture promotes the gastrointestinal motility of diabetic mice by CNP/NPR-B-cGMP and PDE3A-cGMP signaling. Neurogastroenterology and motility 12 30672071
2018 Lack of microRNA-155 ameliorates renal fibrosis by targeting PDE3A/TGF-β1/Smad signaling in mice with obstructive nephropathy. Cell biology international 12 30080287
2015 Hypertension linked to PDE3A activation. Nature genetics 12 26018892
2020 Hypertension and Brachydactyly Syndrome Associated With Vertebral Artery Malformation Caused by a PDE3A Missense Mutation. American journal of hypertension 10 31549136
2019 High cGMP and low PDE3A activity are associated with oocyte meiotic incompetence. Cell cycle (Georgetown, Tex.) 10 31401933
1998 Cyclic nucleotide PDE-3. Quantitation of PDE-3A and -3B mRNAs in rat tissues by RNase protection assay. Cell biochemistry and biophysics 10 9631238
2018 PDE3A gene screening improves diagnostics for patients with Bilginturan syndrome (hypertension and brachydactyly syndrome). Hypertension research : official journal of the Japanese Society of Hypertension 9 30209282
2017 SFPQ, a multifunctional nuclear protein, regulates the transcription of PDE3A. Bioscience reports 9 28743736
2016 cUMP hydrolysis by PDE3A. Naunyn-Schmiedeberg's archives of pharmacology 9 27975297
2024 First-in-Human Dose-Escalation Study of the First-in-Class PDE3A-SLFN12 Complex Inducer BAY 2666605 in Patients with Advanced Solid Tumors Coexpressing SLFN12 and PDE3A. Clinical cancer research : an official journal of the American Association for Cancer Research 8 39437010
2024 Anagrelide and idarubicin combination induces GSDME-mediated pyroptosis as a potential therapy for high-PDE3A acute myeloid leukemia. Leukemia 7 39406931
2020 Identification and functional study of genetic polymorphisms in cyclic nucleotide phosphodiesterase 3A (PDE3A). Annals of human genetics 7 33249558
2017 Docking and quantitative structure-activity relationship of bi-cyclic heteroaromatic pyridazinone and pyrazolone derivatives as phosphodiesterase 3A (PDE3A) inhibitors. PloS one 7 29216268
2015 Charting the interactome of PDE3A in human cells using an IBMX based chemical proteomics approach. Molecular bioSystems 7 26205238
2024 A PDE3A-SLFN12 Molecular Glue Exhibits Significant Antitumor Activity in TKI-Resistant Gastrointestinal Stromal Tumors. Clinical cancer research : an official journal of the American Association for Cancer Research 6 38864850
2024 Velcrin molecular glues induce apoptosis in glioblastomas with high PDE3A and SLFN12 expression. Neuro-oncology advances 6 39166256
2014 PDE3A-SLCO1C1 locus is associated with response to anti-tumor necrosis factor therapy in psoriatic arthritis. Pharmacogenomics 6 25493569
1992 Insulin and isoproterenol induce phosphorylation of the particulate cyclic GMP-inhibited, low Km cyclic AMP phosphodiesterase (cGI PDE) in 3T3-L1 adipocytes. Biochemical and biophysical research communications 6 1314573
2024 Discovery of BAY 2666605, a Molecular Glue for PDE3A and SLFN12. ACS medicinal chemistry letters 5 39411532
2024 Pde3a and Pde3b regulation of murine pulmonary artery smooth muscle cell growth and metabolism. Physiological reports 5 39435735
2016 Synthesis of linear and angular aryl-morpholino-naphth-oxazines, their DNA-PK, PI3K, PDE3A and antiplatelet activity. Bioorganic & medicinal chemistry letters 5 27765510
2024 ALDOA coordinates PDE3A through the β-catenin/ID3 axis to stimulate cancer metastasis and M2 polarization in lung cancer with EGFR mutations. Biochemical and biophysical research communications 4 38244313
2023 PDE3A and GSK3B as Atrial Fibrillation Susceptibility Genes in the Chinese Population via Bioinformatics and Genome-Wide Association Analysis. Biomedicines 4 36979891
2023 PDE3A Is a Highly Expressed Therapy Target in Myxoid Liposarcoma. Cancers 4 38001568
2019 PDE3A variant associated with hypertension and brachydactyly syndrome in a patient with ischemic stroke caused by spontaneous intracranial artery dissection: A review of the clinical and molecular genetic features. European journal of medical genetics 4 31589936
2017 Synthesis and biological evaluation of 8-aryl-2-morpholino-7-O-substituted benzo[e][1,3]oxazin-4-ones against DNA-PK, PI3K, PDE3A enzymes and platelet aggregation. Bioorganic & medicinal chemistry 4 28838830
2023 CRISPR/Cas9 Knock-Out in Primary Neonatal and Adult Cardiomyocytes Reveals Distinct cAMP Dynamics Regulation by Various PDE2A and PDE3A Isoforms. Cells 3 37296663
2020 Whole-exome sequencing identifies a de novo PDE3A variant causing autosomal dominant hypertension with brachydactyly type E syndrome: a case report. BMC medical genetics 2 32631253
2025 PDE3A as a Therapeutic Target for the Modulation of Compartmentalised Cyclic Nucleotide-Dependent Signalling. Cells 1 40497949
2025 IGF2BP3 Modulates mRNA Splicing and Stability to Promote Trophoblast Progression via Interaction with PDE3A and Suppression by miR-196a-5p in Preeclampsia. Biomedicines 1 40563987
2026 AR-mediated YBX3 suppresses oocyte meiotic resumption in polycystic ovary syndrome by attenuating Pde3A and Ccnb1 expression. Journal of ovarian research 0 41673703
2026 The Role of PDE3A in Cancer. ACS omega 0 41726589
2024 RETRACTION: Lack of MicroRNA-155 Ameliorates Renal Fibrosis by Targeting PDE3A/TGF-β1/Smad Signaling in Mice with Obstructive Nephropathy. Cell biology international 0 38845116