Affinage

PDE3B

cGMP-inhibited 3',5'-cyclic phosphodiesterase 3B · UniProt Q13370

Length
1112 aa
Mass
124.3 kDa
Annotated
2026-06-10
43 papers in source corpus 24 papers cited in narrative 25 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 10/10 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PDE3B is a membrane-associated cyclic nucleotide phosphodiesterase that hydrolyzes compartmentalized cAMP pools to integrate hormonal and inflammatory signals controlling lipolysis, glucose handling, insulin secretion, and cardiovascular function (PMID:26031333, PMID:17324123). Unlike the cytosolic PDE3A, PDE3B partitions exclusively to membrane fractions and is enriched in caveolae through association with caveolin-1, which acts as a scaffold for its localization and activation in lipid raft microdomains (PMID:9884079, PMID:16503395). Insulin activates PDE3B downstream of the insulin receptor/PI3K axis: PI3K-associated serine kinase activity phosphorylates and activates PDE3B (PMID:10744689), and insulin drives assembly of large macromolecular complexes at ER/Golgi membranes containing PDE3B together with IRS-1/2, PI3K p85, PKB/Akt, HSP90, and 14-3-3, requiring the PDE3B N-terminal region for recruitment (PMID:17324123). This activation underlies insulin's anti-lipolytic action through PDE3B-dependent cAMP hydrolysis, although direct Akt phosphorylation of PDE3B at S273 is dispensable for this effect (PMID:26031333). Different stimuli target distinct pools: insulin preferentially activates ER/Golgi-resident PDE3B while β3-adrenergic signaling activates caveolar PDE3B in a caveolin-1-dependent manner (PMID:19747167), and biosensor measurements place insulin-activated PDE3B as the dominant controller of cytoplasmic cAMP (PMID:41082906). PDE3B activity is reversed by PP2A, which dephosphorylates and deactivates the enzyme (PMID:10417351), and its protein level is stabilized by ABHD15, loss of which lowers PDE3B and produces insulin resistance (PMID:29768196). The inflammatory kinases IKKε and TBK1 also phosphorylate and activate PDE3B in adipocytes to attenuate β-adrenergic catecholamine signaling (PMID:24368730). Beyond adipose, PDE3B localizes to pancreatic β-cell secretory granules where it restrains depolarization-induced insulin secretion (PMID:17368848), and isoform-specific knockout studies establish roles in cardioprotection against ischemia/reperfusion injury via cAMP/PKA and mitochondrial K-channel signaling (PMID:25877153), endothelial angiogenic sprouting through a perinuclear PKA pool (PMID:31176020), and NLRP3 inflammasome and atherosclerosis control (PMID:27321128). Pde3b transcription is driven by CREB during adipocyte differentiation (PMID:16702214) and by ESRRG in airway epithelium (PMID:40153608). Structurally, the catalytic domain residue W1072 governs inhibitor binding distinct from substrate hydrolysis (PMID:12878217), and PDE3B also hydrolyzes cUMP in a milrinone-sensitive manner (PMID:29808231).

Mechanistic history

Synthesis pass · year-by-year structured walk · 21 steps
  1. 1998 Medium

    Established that PDE3B is distinguished from its paralog PDE3A by exclusive membrane localization, defining it as a particulate enzyme positioned to control local cAMP.

    Evidence Subcellular fractionation and isoform-selective immunoblotting across rat tissues and vascular smooth muscle cells

    PMID:9884079

    Open questions at the time
    • Did not identify the membrane anchor or microdomain
    • Single lab, antibody-based
  2. 1999 Medium

    Identified the phosphatase arm of PDE3B regulation by showing PP2A deactivates the enzyme, framing PDE3B activity as a reversible phosphorylation switch.

    Evidence Phosphatase inhibitor pharmacology, MonoQ co-purification, and in vitro dephosphorylation assays in rat adipocytes

    PMID:10417351

    Open questions at the time
    • Did not map the dephosphorylated residues
    • PP2A targeting/recruitment mechanism unknown
  3. 2000 Medium

    Linked insulin receptor signaling to PDE3B by showing PI3K-associated serine kinase activity phosphorylates and activates PDE3B, providing a biochemical basis for insulin's anti-lipolytic effect.

    Evidence PI3K activity assays, anti-PDE3B immunoprecipitation, serine phosphorylation measurement, and wortmannin in human adipocytes

    PMID:10744689

    Open questions at the time
    • Did not identify the terminal kinase or phosphosites
    • Correlative link between phosphorylation and activation
  4. 2003 High

    Defined the catalytic-domain determinant W1072 that separates inhibitor binding from substrate hydrolysis, informing the pharmacology of PDE3B-selective compounds.

    Evidence Recombinant active-site mutagenesis, enzyme kinetics, and homology modeling

    PMID:12878217

    Open questions at the time
    • Only two mutations tested
    • No full crystal structure in this study
  5. 2006 High

    Localized plasma-membrane PDE3B to caveolae via caveolin-1 association, identifying the structural basis for its membrane targeting.

    Evidence Detergent-resistance, sucrose gradients, co-IP with caveolin-1, and caveolin-1 KO mice in adipocytes

    PMID:16503395

    Open questions at the time
    • Did not resolve whether caveolin-1 binding is direct
    • Role in non-adipose tissues untested here
  6. 2006 Medium

    Tested whether PI3Kγ scaffolding subunit p87PIKAP couples PI3Kγ to PDE3B, establishing a physical interaction but not functional reconstitution.

    Evidence Co-immunoprecipitation and heterologous expression in HEK293 cells

    PMID:16476736

    Open questions at the time
    • Functional reconstitution was negative
    • Single-lab co-IP without reciprocal in vivo validation
  7. 2006 High

    Identified CREB as the transcription factor driving Pde3b induction during adipocyte differentiation, connecting cAMP signaling to PDE3B gene expression.

    Evidence Pde3b promoter luciferase reporters, ChIP, and dominant-negative CREB in 3T3-L1 cells

    PMID:16702214

    Open questions at the time
    • Did not address regulation in mature adipocytes
    • Other promoter inputs not excluded
  8. 2007 High

    Resolved the molecular architecture of insulin activation by showing PDE3B is recruited into Akt/IRS/PI3K macromolecular complexes at ER/Golgi membranes via its N-terminal region.

    Evidence Subcellular fractionation, gel filtration, co-IP, siRNA, truncation mutants, and confocal microscopy in adipocytes

    PMID:17324123

    Open questions at the time
    • Did not pinpoint the direct binding partner within the complex
    • Stoichiometry and assembly order unresolved
  9. 2007 High

    Extended PDE3B function to pancreatic β-cells, establishing it as a brake on depolarization-induced insulin secretion via cAMP hydrolysis at secretory granules.

    Evidence Transgenic and KO mice, adenoviral overexpression in INS-1 cells, electron microscopy, and capacitance electrophysiology

    PMID:17368848

    Open questions at the time
    • Granule-targeting mechanism not defined
    • Relationship to caveolar pool unclear
  10. 2009 High

    Demonstrated stimulus-specific compartmentalization: insulin activates ER/Golgi PDE3B while β3-adrenergic signaling activates caveolar PDE3B in a caveolin-1-dependent manner.

    Evidence Fractionation, caveolin-1 siRNA and KO mice, gel filtration, and phosphorylation/lipolysis readouts in adipocytes

    PMID:19747167

    Open questions at the time
    • How a single enzyme is differentially routed remains unresolved
    • Kinetics of inter-pool exchange unknown
  11. 2013 High

    Identified IKKε/TBK1 as inflammatory kinases that phosphorylate and activate PDE3B, linking obesity-associated inflammation to catecholamine resistance.

    Evidence Overexpression/inhibitor studies in 3T3-L1 cells and amlexanox treatment of obese mice with cAMP and lipolysis readouts

    PMID:24368730

    Open questions at the time
    • Direct phosphosites not mapped in this study
    • Whether activation is direct vs. via intermediaries
  12. 2015 High

    Showed PDE3B is required for insulin's anti-lipolytic action but that the major Akt site S273 is dispensable, refining the phosphorylation model.

    Evidence PDE3B KO brown adipocytes reconstituted with wild-type and S273A mutant; glycerol release assays

    PMID:26031333

    Open questions at the time
    • The functionally critical phosphosite(s) remain unidentified
    • Did not test combinatorial mutants
  13. 2015 High

    Established an isoform-specific cardioprotective role for PDE3B in ischemia/reperfusion, acting through cAMP/PKA and mitochondrial K-channel signaling.

    Evidence PDE3B vs PDE3A KO mice, in vivo/in vitro I/R models, proteomics, and mitochondrial assays

    PMID:25877153

    Open questions at the time
    • Mechanism linking PDE3B to mitochondrial protein enrichment not fully defined
    • Caveolin-3 dependence not directly tested
  14. 2017 Medium

    Showed PDE3B loss drives white-to-beige adipocyte conversion via cAMP/PKA and AMPK activation, connecting the enzyme to whole-body energy expenditure.

    Evidence Pde3b KO mice with metabolic phenotyping, β-oxidation, and oxygen consumption measurements

    PMID:28084425

    Open questions at the time
    • Adipocyte-autonomous vs systemic effects not separated
    • Direct PKA/AMPK targets not mapped
  15. 2016 Medium

    Linked PDE3B to innate immunity and atherosclerosis by showing its ablation suppresses NLRP3 inflammasome activation and plaque formation.

    Evidence PDE3B KO and double-KO mice (apoE-/-, LDL-R-/-) with cytokine, gene expression, and plaque readouts

    PMID:27321128

    Open questions at the time
    • Cell type driving the inflammasome effect unresolved
    • Mechanistic link from cAMP to NLRP3 not defined
  16. 2018 High

    Identified ABHD15 as a binding partner that stabilizes PDE3B protein, establishing post-translational control of PDE3B abundance as a node in insulin sensitivity.

    Evidence Abhd15 KO mice, co-IP, and PDE3B/lipolysis/HSL readouts

    PMID:29768196

    Open questions at the time
    • Structural basis of stabilization unknown
    • Whether ABHD15 binding is direct vs complex-mediated
  17. 2018 Medium

    Demonstrated PDE3B hydrolyzes cUMP in a milrinone-sensitive manner, broadening its substrate repertoire beyond cAMP/cGMP.

    Evidence Recombinant enzyme kinetics, HPLC-MS substrate quantitation, and docking on PDB 1SO2

    PMID:29808231

    Open questions at the time
    • Physiological role of cUMP hydrolysis untested
    • Low affinity questions in vivo relevance
  18. 2019 Medium

    Established an isoform-specific role for PDE3B in endothelial angiogenic sprouting by antagonizing a perinuclear PKA pool that controls podosome biogenesis and cdc42 activity.

    Evidence PDE3B vs PDE3A siRNA, sprouting assays, co-IP with PKA, and subcellular PKA activity imaging

    PMID:31176020

    Open questions at the time
    • Mechanism of perinuclear targeting unresolved
    • Whether PDE3B-PKA interaction is direct
  19. 2024 Medium

    Implicated PDE3B in organ preservation injury, where its elevation triggers AMPK-dependent autophagy and liver damage reversible by pharmacological inhibition.

    Evidence Multi-omics and cilostamide treatment across rat, pig, and human supercooled liver preservation models

    PMID:39602509

    Open questions at the time
    • Upstream driver of PDE3B elevation unknown
    • Single study
  20. 2025 Medium

    Defined the cAMP pool controlled by PDE3B at subcellular resolution, placing insulin-activated PDE3B as the dominant regulator of cytoplasmic cAMP distinct from plasma-membrane and lipid-droplet pools.

    Evidence Compartment-targeted EPAC1-FRET biosensors and PDE inhibitor pharmacology in 3T3-L1 adipocytes

    PMID:41082906

    Open questions at the time
    • Does not explain how compartment specificity is achieved
    • Single lab
  21. 2025 Medium

    Identified ESRRG as a direct transcriptional activator of Pde3b in airway epithelium, extending PDE3B transcriptional control to inflammatory airway disease.

    Evidence Luciferase reporter, ChIP-PCR, AAV-shEsrrg silencing, and pharmacological inhibition in vivo

    PMID:40153608

    Open questions at the time
    • Generality beyond airway epithelium untested
    • Interaction with CREB-driven regulation unclear

Open questions

Synthesis pass · forward-looking unresolved questions
  • The functionally critical phosphosite(s) and the direct kinase(s)/binding partners that mediate compartment-specific activation of PDE3B remain undefined.
  • S273-independent activating phosphorylation not mapped
  • Direct interactor within the insulin macromolecular complex unidentified
  • Mechanism routing one enzyme to distinct membrane pools unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016787 hydrolase activity 2 GO:0140098 catalytic activity, acting on RNA 2
Localization
GO:0005886 plasma membrane 3 GO:0005783 endoplasmic reticulum 2 GO:0005794 Golgi apparatus 2 GO:0031410 cytoplasmic vesicle 1
Pathway
R-HSA-162582 Signal Transduction 4 R-HSA-1430728 Metabolism 3 R-HSA-168256 Immune System 1
Partners
ABHD15AKT1CAV1IRS1IRS2PIK3R1PRKACA
Complex memberships
caveolaeinsulin-induced ER/Golgi macromolecular signaling complex (PDE3B/IRS/PI3K/Akt/HSP90/14-3-3)

Evidence

Reading pass · 25 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2013 IKKε and TBK1 phosphorylate and activate PDE3B in adipocytes, thereby reducing cAMP levels and attenuating β-adrenergic/catecholamine signaling and lipolysis; specific inhibition of these kinases with amlexanox reversed obesity-induced catecholamine resistance and restored PKA signaling in vivo. Overexpression and inhibitor studies in 3T3-L1 adipocytes; in vivo treatment of obese mice with amlexanox; measurement of cAMP, lipolysis, HSL phosphorylation, and UCP1 induction eLife High 24368730
2015 PDE3B is required for insulin's anti-lipolytic action in adipocytes, as PDE3B knockout adipocytes fail to suppress β-adrenergic receptor-stimulated glycerol release in response to insulin; however, reexpression of a PDE3B mutant ablating the major Akt phosphorylation site (S273) still rescues insulin's anti-lipolytic effect, demonstrating that direct Akt phosphorylation of PDE3B at S273 is not required for this action. PDE3B knockout brown adipocytes; adenoviral reexpression of wild-type and S273A mutant PDE3B; glycerol release assay Molecular and cellular biology High 26031333
2006 The novel PI3Kγ regulatory subunit p87PIKAP physically interacts with PDE3B, suggesting p87PIKAP participates in the noncatalytic scaffolding interaction of PI3Kγ p110γ with PDE3B; however, coexpression of PDE3B with PI3Kγ subunits alone was not sufficient to reconstitute the regulatory effect of PI3Kγ on PDE3B activity observed in heart. Co-immunoprecipitation; heterologous expression in HEK293 cells The Journal of biological chemistry Medium 16476736
1998 PDE3B (135 kDa) is exclusively localized to the particulate (membrane) fraction in all rat tissues and cultured vascular smooth muscle cells examined, in contrast to PDE3A which is cytosolic; prolonged cAMP elevation increases PDE3B protein and particulate PDE3 activity. Subcellular fractionation; immunoblotting with PDE3B-selective antisera; RT-PCR British journal of pharmacology Medium 9884079
2000 Phosphatidylinositol 3-kinase serine kinase activity associated with the insulin receptor phosphorylates PDE3B (the 135-kDa protein) in human adipocytes, and this phosphorylation is associated with PDE3B activation and the antilipolytic effect of insulin. PI3K activity assay; immunoprecipitation with anti-PDE3B; serine phosphorylation measurement; PI3K inhibitor wortmannin The Journal of biological chemistry Medium 10744689
1999 Protein phosphatase 2A (PP2A) dephosphorylates and deactivates PDE3B in rat adipocytes; PP2A co-purifies with PDE3B phosphatase activity, and okadaic acid (which selectively inhibits PP2A over PP1 at 1 µM) activates PDE3B in vivo, while tautomycin (PP1-selective) does not. Phosphatase inhibitor treatment in adipocytes; MonoQ chromatography co-purification; 32P phosphorylation assays; in vitro dephosphorylation assay The Biochemical journal Medium 10417351
2007 Insulin induces formation of large macromolecular complexes at ER/Golgi and plasma membrane fractions of adipocytes containing phosphorylated/activated PDE3B together with IRS-1, IRS-2, PI3K p85, PKB/Akt, HSP90, and 14-3-3; the N-terminal region of PDE3B (first 604 amino acids) is required for insulin-induced activation and recruitment into these complexes; PDE3B co-immunoprecipitates preferentially with phosphorylated/activated PKB. Subcellular fractionation; Superose 6 gel filtration; co-immunoprecipitation; siRNA knockdown; recombinant truncation mutants; confocal microscopy; PI3K inhibitors The Biochemical journal High 17324123
2009 Insulin preferentially phosphorylates/activates PDE3B in internal membrane (ER/Golgi) compartments, whereas the β3-adrenergic agonist CL316243 preferentially activates PDE3B in caveolae; caveolin-1 knockdown abolishes CL316243-mediated PDE3B activation and lipolysis signaling, implicating cav-1 as a chaperone/scaffold for PDE3B in lipid raft microdomains. Subcellular fractionation; siRNA knockdown of caveolin-1; Cav-1 KO mouse adipocytes; Superose 6 gel filtration; 32P phosphorylation; HSL and perilipin phosphorylation The Biochemical journal High 19747167
2006 Plasma membrane PDE3B in adipocytes is associated with caveolae, co-eluting with caveolin-1, flotillin-1, and cholesterol; disruption of caveolae (by methyl-β-cyclodextrin or caveolin-1 deficiency) reduces membrane-associated PDE3B activity; PDE3B co-immunoprecipitates with caveolin-1. Subcellular fractionation; detergent-resistance assay; Superose-6 chromatography; sucrose density gradient; co-immunoprecipitation; caveolin-1 KO mice; methyl-β-cyclodextrin treatment Cellular signalling High 16503395
2005 PDE3B (but not PDE4) contributes to insulin-induced glucose uptake, GLUT-4 translocation to the plasma membrane, and lipogenesis in rat primary adipocytes; PDE3 inhibition reduces GLUT-4 translocation to caveolae; this regulation appears to involve a cAMP/Epac (not PKA) signaling mechanism, as H89 (PKA inhibitor) did not reverse the effect but an Epac agonist mimicked it. PDE3 and PDE4 selective inhibitors (OPC3911, milrinone, RO 20-1724); glucose uptake assays; GLUT-4 translocation measurement; PKA activity; lipolysis assay; Epac agonist; H89 Cellular signalling Medium 15961276
2007 Insulin regulates adiponectin and leptin secretion and expression through a PI3K-PDE3B-cAMP pathway; PDE3 inhibition (milrinone) or PI3K inhibitors block the ability of insulin to restore β-agonist/cAMP-suppressed adiponectin and leptin production in primary rat adipocytes. PDE3 inhibitor (milrinone); PI3K inhibitors; cAMP analogues; adiponectin/leptin ELISA in primary rat adipocytes The Biochemical journal Medium 17286556
2007 PDE3B localizes to insulin secretory granules and plasma membrane in pancreatic β-cells; overexpression of PDE3B reduces first-phase Ca2+-triggered exocytosis and granule mobilization, while PDE3B KO increases K+-stimulated insulin secretion, establishing PDE3B as a regulator of depolarization-induced insulin secretion via cAMP hydrolysis. Transgenic RIP-PDE3B/7 mice; PDE3B KO mice; adenoviral PDE3B overexpression in INS-1 cells; subcellular fractionation; confocal microscopy; transmission electron microscopy; voltage-clamp capacitance measurements Cellular signalling High 17368848
2015 Targeted disruption of PDE3B (but not PDE3A) protects mouse heart from ischemia/reperfusion injury, reducing infarct size and improving cardiac function; the cardioprotective effect requires cAMP/PKA signaling and mitochondrial calcium-activated K channel opening; PDE3B KO mitochondria are enriched in Bcl-2, produce less ROS, and accumulate cardioprotective proteins in caveolin-3-enriched fractions (ICEFs) in a PKA-dependent manner; PDE3B was localized with caveolin-3 at transverse tubules. PDE3B and PDE3A KO mice; in vivo and in vitro I/R models; infarct size measurement; PKA inhibitor; paxilline (mito K-channel blocker); proteomics; mitochondrial fractionation; ROS measurement; mitochondrial permeability transition pore assay Proceedings of the National Academy of Sciences of the United States of America High 25877153
2018 ABHD15 associates with and stabilizes PDE3B protein; loss of ABHD15 decreases PDE3B expression in white adipose tissue, resulting in elevated PKA activity, increased HSL phosphorylation, and failure of insulin to suppress lipolysis, leading to insulin resistance. Abhd15 global and conditional KO mice; in vitro co-immunoprecipitation; PDE3B protein quantification; AKT phosphorylation; glucose uptake; lipolysis assay; HSL phosphorylation Cell reports High 29768196
2003 Tryptophan 1072 in the catalytic domain of human PDE3B is critical for inhibitor binding but not substrate hydrolysis; W1072A mutation caused 158-fold decrease in cilostamide affinity and 740-fold decrease in cGMP affinity, but only ~7-fold increase in cAMP Km, demonstrating that the inhibitor binding region is distinct from but overlapping with the substrate binding region. Recombinant PDE3B expression in E. coli; active-site mutagenesis (W1072A, W1072Y); enzyme kinetic assays; inhibitor binding assays; homology modeling based on PDE4B crystal structure Biochemical and biophysical research communications High 12878217
2018 PDE3B hydrolyzes cUMP with low affinity (Km ~550 µM) and high velocity (Vmax ~76 µmol/min/mg) in a milrinone-sensitive manner; docking studies using the PDE3B crystal structure show uracil 3-NH forms one hydrogen bond with Q988, whereas cAMP forms two hydrogen bonds; the milrinone-sensitive cUMP-hydrolytic activity previously observed in rat adipose tissue is attributable to PDE3B. Recombinant PDE3B enzyme kinetics; HPLC-tandem MS substrate/product quantitation; milrinone inhibition assay; molecular docking with crystal structure PDB 1SO2; adipocyte lysate and rat adipose tissue membrane assays Naunyn-Schmiedeberg's archives of pharmacology Medium 29808231
2006 CREB and phospho-CREB bind to cAMP-response elements in both distal and proximal promoter regions of the Pde3b gene and are required for IBMX-induced transcriptional upregulation of PDE3B during 3T3-L1 preadipocyte differentiation; dominant-negative CREB markedly inhibits Pde3b mRNA and protein induction. Luciferase reporter assays with Pde3b promoter fragments; dominant-negative CREB; chromatin immunoprecipitation (ChIP) with anti-CREB, anti-phospho-CREB, anti-CBP/p300; real-time PCR; immunoblotting The Journal of biological chemistry High 16702214
2015 G-CSF activates a JAK2/PI3K/PDE3B signaling pathway in adrenal cortical cells, leading to cAMP degradation and inhibition of corticosterone synthesis; PDE3B inhibition in vivo reverses the neuroprotective effects of G-CSF in a neonatal hypoxic-ischemic brain injury rat model. Western blot for JAK2/PI3K/Akt/PDE3B in Y1 adrenal cells; cAMP and corticosterone ELISA; PDE3B inhibitor in vivo; neonatal HI rat model with TTC staining Experimental neurology Medium 25816736
2017 PDE3B knockout in mouse WAT leads to activation of cAMP/PKA and AMPK signaling pathways, resulting in white-to-beige adipocyte conversion ('browning') with increased β-oxidation and oxygen consumption under high-fat diet conditions. Targeted Pde3b gene inactivation (KO mice); cAMP/PKA and AMPK pathway analysis; metabolic phenotyping; β-oxidation assay; oxygen consumption measurement Scientific reports Medium 28084425
2016 PDE3B ablation in white adipose tissue prevents NLRP3 inflammasome activation by reducing expression of NLRP3, caspase-1, ASC, AIM2, TNFα, and IL-1β; signaling cascades including SMAD, NFAT, NFκB, and MAP kinases are modulated in PDE3B KO WAT; PDE3B KO also reduces atherosclerotic plaque formation in apoE-/- and LDL-R-/- backgrounds. PDE3B KO mice; LPS injection model; serum cytokine measurement; gene expression analysis; double KO mice (apoE-/-/PDE3B-/-; LDL-R-/-/PDE3B-/-); aortic plaque quantification Scientific reports Medium 27321128
2019 PDE3B (but not PDE3A) silencing impairs endothelial cell angiogenic sprouting; PDE3B and PKA co-localize in a perinuclear region in human endothelial cells and can be co-immunoprecipitated; PDE3B silencing activates the perinuclear pool of PKA; PDE3B antagonizes anti-angiogenic PKA actions by controlling cAMP levels that regulate podosome rosette biogenesis, matrix degradation, and cdc42 activity. siRNA silencing of PDE3B vs. PDE3A; in vitro and ex vivo angiogenesis sprouting assays; cilostamide pharmacology; PKA inhibitor; co-immunoprecipitation; subcellular PKA activity imaging; cdc42 activity assay Cellular signalling Medium 31176020
2024 PDE3B elevation during supercooling liver preservation promotes cAMP reduction, triggering AMPK-dependent autophagy that leads to liver injury; cilostamide (PDE3B inhibitor) blocks this pathway, inhibits autophagy, and substantially ameliorates liver injury in rat, pig, and human liver models. Integrative metabolomics, transcriptomics, and proteomics; cilostamide treatment in rat, pig, and human liver SLP models; cAMP measurement; AMPK-autophagy pathway analysis Science translational medicine Medium 39602509
2024 Crystal structure re-analysis of PDE3B complexed with boronic acid inhibitor GSK4394835A reveals that H737 undergoes nucleophilic addition to the boronic acid moiety, generating a tetrahedral boronate anion covalently bound in the PDE3B active site, establishing GSK4394835A as a reversible covalent inhibitor. Re-refinement of X-ray crystal structure (PDB 8SYC) with reprocessed structure factor amplitudes; electron density map analysis; crystallographic refinement bioRxivpreprint Medium
2025 In adipocytes, insulin-activated PDE3B predominantly regulates cytoplasmic cAMP pools, while FGF1/PDE4D primarily regulates plasma membrane cAMP; neither pathway affects a distinct lipid droplet-associated cAMP pool detected by a novel perilipin-1-EPAC1-FRET biosensor. EPAC1-based FRET cAMP biosensors targeted to cytoplasm, plasma membrane, or lipid droplets (perilipin-1 fusion); PDE inhibitor pharmacology; live-cell imaging in 3T3-L1 adipocytes British journal of pharmacology Medium 41082906
2025 Esrrg (estrogen-related receptor-γ) binds directly to the Pde3b promoter and transcriptionally activates Pde3b expression in airway epithelial cells; Esrrg inhibition reduces PDE3B expression and ameliorates PM2.5-aggravated airway inflammation. Dual luciferase reporter assay; chromatin immunoprecipitation PCR (ChIP-PCR); AAV-shEsrrg silencing in vivo; pharmacological Esrrg inhibition (GSK5182); mRNA sequencing American journal of respiratory cell and molecular biology Medium 40153608

Source papers

Stage 0 corpus · 43 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2013 Inflammation produces catecholamine resistance in obesity via activation of PDE3B by the protein kinases IKKε and TBK1. eLife 135 24368730
2011 From PDE3B to the regulation of energy homeostasis. Current opinion in pharmacology 117 22001403
2006 Characterization of p87PIKAP, a novel regulatory subunit of phosphoinositide 3-kinase gamma that is highly expressed in heart and interacts with PDE3B. The Journal of biological chemistry 107 16476736
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 The Role of PDE3B Phosphorylation in the Inhibition of Lipolysis by Insulin. Molecular and cellular biology 84 26031333
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 74 25877153
2005 Role of PDE3B in insulin-induced glucose uptake, GLUT-4 translocation and lipogenesis in primary rat adipocytes. Cellular signalling 59 15961276
2000 Phosphorylation of PDE3B by phosphatidylinositol 3-kinase associated with the insulin receptor. The Journal of biological chemistry 58 10744689
1996 Characterization of the cDNA and gene encoding human PDE3B, the cGIP1 isoform of the human cyclic GMP-inhibited cyclic nucleotide phosphodiesterase family. Genomics 56 8884271
2002 Inhibition of PDE3B augments PDE4 inhibitor-induced apoptosis in a subset of patients with chronic lymphocytic leukemia. Clinical cancer research : an official journal of the American Association for Cancer Research 54 11839681
2007 Regulation of adiponectin and leptin secretion and expression by insulin through a PI3K-PDE3B dependent mechanism in rat primary adipocytes. The Biochemical journal 53 17286556
1999 Phosphorylation and activation of phosphodiesterase type 3B (PDE3B) in adipocytes in response to serine/threonine phosphatase inhibitors: deactivation of PDE3B in vitro by protein phosphatase type 2A. The Biochemical journal 53 10417351
2007 Insulin-induced formation of macromolecular complexes involved in activation of cyclic nucleotide phosphodiesterase 3B (PDE3B) and its interaction with PKB. The Biochemical journal 45 17324123
2009 Differential regulation of adipocyte PDE3B in distinct membrane compartments by insulin and the beta3-adrenergic receptor agonist CL316243: effects of caveolin-1 knockdown on formation/maintenance of macromolecular signalling complexes. The Biochemical journal 42 19747167
2018 Loss of ABHD15 Impairs the Anti-lipolytic Action of Insulin by Altering PDE3B Stability and Contributes to Insulin Resistance. Cell reports 41 29768196
2006 Plasma membrane cyclic nucleotide phosphodiesterase 3B (PDE3B) is associated with caveolae in primary adipocytes. Cellular signalling 41 16503395
2017 White to beige conversion in PDE3B KO adipose tissue through activation of AMPK signaling and mitochondrial function. Scientific reports 36 28084425
2018 Astragaloside IV Inhibits Adipose Lipolysis and Reduces Hepatic Glucose Production via Akt Dependent PDE3B Expression in HFD-Fed Mice. Frontiers in physiology 32 29410630
2016 Phosphodiesterase 3B (PDE3B) regulates NLRP3 inflammasome in adipose tissue. Scientific reports 28 27321128
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
2021 CircSCAP Aggravates Oxidized Low-density Lipoprotein-induced Macrophage Injury by Upregulating PDE3B by miR-221-5p in Atherosclerosis. Journal of cardiovascular pharmacology 22 34321402
2007 Beta-cell PDE3B regulates Ca2+-stimulated exocytosis of insulin. Cellular signalling 20 17368848
2000 Cardiac type cGMP-inhibited phosphodiesterase (PDE3A) gene structure: similarity and difference to adipocyte type PDE3B gene. Biochemical and biophysical research communications 15 10679291
2015 Granulocyte-colony stimulating factor activates JAK2/PI3K/PDE3B pathway to inhibit corticosterone synthesis in a neonatal hypoxic-ischemic brain injury rat model. Experimental neurology 13 25816736
2020 Diosgenin Inhibits Excessive Proliferation and Inflammatory Response of Synovial Fibroblasts in Rheumatoid Arthritis by Targeting PDE3B. Inflammation 12 33237390
2006 Importance of cAMP-response element-binding protein in regulation of expression of the murine cyclic nucleotide phosphodiesterase 3B (Pde3b) gene in differentiating 3T3-L1 preadipocytes. The Journal of biological chemistry 12 16702214
2024 PDE3B regulates KRT6B and increases the sensitivity of bladder cancer cells to copper ionophores. Naunyn-Schmiedeberg's archives of pharmacology 11 38165426
2015 Leptin receptor expressing neurons express phosphodiesterase-3B (PDE3B) and leptin induces STAT3 activation in PDE3B neurons in the mouse hypothalamus. Peptides 11 26297880
2019 Phosphodiesterase 3B (PDE3B) antagonizes the anti-angiogenic actions of PKA in human and murine endothelial cells. Cellular signalling 8 31176020
2024 Discovery and SAR Study of Boronic Acid-Based Selective PDE3B Inhibitors from a Novel DNA-Encoded Library. Journal of medicinal chemistry 7 38284310
2023 Hsa_circ_0007707 participates in PDE3B-mediated apoptosis inhibition and inflammation promotion in fibroblast-like synoviocytes. International immunopharmacology 7 37086679
2003 The role of tryptophan 1072 in human PDE3B inhibitor binding. Biochemical and biophysical research communications 7 12878217
2024 Pde3a and Pde3b regulation of murine pulmonary artery smooth muscle cell growth and metabolism. Physiological reports 6 39435735
2018 cUMP hydrolysis by PDE3B. Naunyn-Schmiedeberg's archives of pharmacology 6 29808231
2024 Administration of Liposomal-Based Pde3b Gene Therapy Protects Mice Against Collagen-Induced Rheumatoid Arthritis via Modulating Macrophage Polarization. International journal of nanomedicine 5 38774028
2022 Diosgenin reduces phosphodiesterase 3B (PDE3B) through AMP-activated protein kinase/ mechanistic target of rapamycin (AMPK/mTOR) signaling pathway to ameliorate streptozotocin-induced pancreatic β-cell apoptosis and dysfunction. Bioengineered 5 35030973
2000 The mouse Psma1 gene coding for the alpha-type C2 proteasome subunit: structural and functional analysis, mapping, and colocalization with Pde3b on mouse chromosome 7. Genomics 5 10873386
2025 Esrrg Inhibition Protects against Fine Particulate Matter-induced Asthma Aggravation by Reducing Pde3b. American journal of respiratory cell and molecular biology 2 40153608
2022 CircRNA PDE3B regulates tumorigenicity via the miR-136-5p/MAP3K2 axis of esophageal squamous cell carcinoma. Histology and histopathology 2 36533720
2025 miR-135b-5p/PDE3B Axis Regulates Gemcitabine Resistance in Pancreatic Cancer Through Epithelial-Mesenchymal Transition. Molecular carcinogenesis 1 40170518
2025 Clinacanthus nutans (Burm.f.) Lindau facilitates cuproptosis and ameliorates colon cancer progression by inhibiting PDE3B-mediated Apelin pathway. Discover oncology 1 40788438
2024 Targeting the PDE3B-cAMP-autophagy axis prevents liver injury in long-term supercooling liver preservation. Science translational medicine 1 39602509
2025 PDE4D and PDE3B orchestrate distinct cAMP microdomains in 3T3-L1 adipocytes. British journal of pharmacology 0 41082906

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