Affinage

ADRB2

Beta-2 adrenergic receptor · UniProt P07550

Length
413 aa
Mass
46.5 kDa
Annotated
2026-06-09
100 papers in source corpus 20 papers cited in narrative 20 extracted findings
Cross-family judge vs UniProt: tie faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ADRB2 (β2-adrenergic receptor) is a catecholamine-responsive G-protein-coupled receptor whose signaling output is reused across metabolic, immune, skeletal, and oncogenic contexts to control autophagy, transcription, cell proliferation, and protein stability (PMID:27154061, PMID:31624248, PMID:40466637). Through Akt-dependent signaling, ADRB2 disrupts the Beclin1/VPS34/Atg14 complex to suppress autophagy and stabilize HIF1α, reprogramming glucose metabolism and conferring sorafenib resistance in hepatocellular carcinoma (PMID:27154061); in a context-dependent manner its activation can instead restore autophagy-lysosomal function by upregulating VMA21/V-ATPase to mitigate amyloid-β pathology (PMID:37964627). In cancer cells, agonist-stimulated ADRB2 drives proliferation, invasion, and metastasis through the ERK1/2-JNK-MAPK cascade and the transcription factors NF-κB, AP-1, CREB, and STAT3 (PMID:31624248), and through ADRB2/VEGFR2 interaction and a CREB/PSAT1 axis it promotes resistance to VEGFR2-targeted therapy (PMID:35075132). Through PKA-driven CREB phosphorylation it enhances PPARγ expression and lipid synthesis (PMID:36012741), and through Gi coupling it transduces inhibitory signaling whose efficiency is allele-dependent (PMID:30374408). ADRB2 protein levels are set post-translationally: PHD3 binding destabilizes the receptor (PMID:28939592), while USP33-mediated deubiquitination stabilizes it and is antagonized by the hepatokine ERAP1 to interrupt insulin signaling in skeletal muscle (PMID:35192681). ADRB2 expression is constrained transcriptionally by the repressor HIC1 (PMID:22194601) and by promoter-proximal SNPs that modulate NF1 and other nuclear-factor binding (PMID:23229733, PMID:29588580), post-transcriptionally by miR-15a-5p targeting its 3'UTR (PMID:31104300), and epigenetically by promoter hypermethylation (PMID:30986742). In immune cells ADRB2 acts as an inhibitory checkpoint, restraining T/CAR-T cell function through a ZAP-70/NF-κB axis (PMID:39228124), while ADRB2+ interstitial macrophages near sympathetic nerves amplify norepinephrine-driven inflammation and lung injury (PMID:40466637). In development and skeletal biology, β-cell ADRB2 restrains islet vascularization by suppressing VEGF-A (PMID:30303066) and mesenchymal-cell ADRB2 promotes osteoclastogenesis and bone remodeling (PMID:25252876, PMID:31926929).

Mechanistic history

Synthesis pass · year-by-year structured walk · 20 steps
  1. 2010 Medium

    Established that whole-gene sequence variation in ADRB2 determines how much receptor reaches the cell surface and how it is downregulated by agonist, framing ADRB2 function as haplotype-dependent.

    Evidence Whole-gene haplotype transfection into COS-7 cells with radioligand binding and agonist-promoted downregulation assays

    PMID:20686604

    Open questions at the time
    • Which individual polymorphisms drive the effect was not resolved
    • No link to downstream signaling consequences
    • Heterologous COS-7 system may not reflect native cell types
  2. 2011 High

    Identified HIC1 as a direct transcriptional repressor of ADRB2, explaining how loss of a tumor suppressor de-represses ADRB2 to drive cancer cell migration and invasion.

    Evidence Promoter luciferase, ChIP and sequential ChIP, siRNA knockdown, and migration/invasion rescue in breast cancer cells

    PMID:22194601

    Open questions at the time
    • Downstream ADRB2 effectors mediating invasion not defined
    • Whether HIC1 acts at the same elements as functional SNPs unknown
  3. 2012 Medium

    Showed a promoter SNP reduces ADRB2 transcription and alters nuclear-factor binding, providing a functional basis for genetic association with obesity.

    Evidence Luciferase reporter comparing alleles and EMSA for nuclear factor binding

    PMID:23229733

    Open questions at the time
    • Identity of the bound nuclear factor not determined
    • Causal link to obesity is associative, not mechanistic in vivo
  4. 2014 High

    Connected mechanical force to ADRB2 induction and bone resorption, showing Adrb2 raises the RANKL/OPG ratio to drive osteoclastogenesis.

    Evidence Compressive force on primary PDLCs, Ca2+ measurement, co-culture osteoclastogenesis, Adrb1/2 knockout mice, ganglionectomy

    PMID:25252876

    Open questions at the time
    • Signaling between ADRB2 and RANKL induction not detailed
    • Cell-autonomy vs. neural contribution incompletely separated
  5. 2016 High

    Defined a mechanism by which ADRB2 suppresses autophagy—disrupting the Beclin1/VPS34/Atg14 complex via Akt—to stabilize HIF1α and confer therapy resistance.

    Evidence Reciprocal Co-IP, immunoblot, knockdown/inhibitor studies in HCC lines and xenografts

    PMID:27154061

    Open questions at the time
    • How ADRB2 activates Akt in this context not resolved
    • Whether autophagy regulation generalizes beyond HCC unknown
  6. 2017 Medium

    Revealed post-translational control of ADRB2 by PHD3, showing that blocking PHD3-ADRB2 interaction stabilizes the receptor to counter muscle atrophy.

    Evidence Co-IP of PHD3-ADRB2, PHD3 inhibition/knockdown, AKG rescue in corticosterone and DMD atrophy models

    PMID:28939592

    Open questions at the time
    • Whether PHD3 hydroxylates ADRB2 directly not established
    • Single lab; reciprocal validation limited
  7. 2018 High

    Demonstrated developmental, sex-specific roles for β-cell ADRB2 in restraining islet vascularization through VEGF-A suppression, linking receptor loss to glucose intolerance.

    Evidence Pancreas-specific conditional Adrb2 knockout, glucose/insulin assays, VEGF-A measurement, VEGFR-blockade rescue

    PMID:30303066

    Open questions at the time
    • Basis of the female-specific phenotype unexplained
    • Signaling linking ADRB2 to VEGF-A repression undefined
  8. 2018 Medium

    Linked the ADRB2 Gly16/Arg16 polymorphism to Gi-coupling efficiency and β-blocker responsiveness, establishing a genotype-dependent signaling determinant of therapy.

    Evidence In vitro Gi-coupling assays plus genotype-stratified multicenter heart-failure cohorts

    PMID:30374408

    Open questions at the time
    • Single mechanistic in vitro assay underpinning the clinical correlation
    • Molecular basis of altered Gi coupling not structurally resolved
  9. 2018 Medium

    Showed an upstream SNP alters NF1 binding and ADRB2 promoter activity, providing an allele-specific transcriptional mechanism tied to COPD susceptibility.

    Evidence Luciferase reporter, ChIP for NF1 binding, and ADRB2 expression in COPD patients

    PMID:29588580

    Open questions at the time
    • Causal contribution to COPD pathophysiology not demonstrated
    • Whether NF1 regulation interacts with other repressors unknown
  10. 2018 Medium

    Identified ADRB2/VEGFR2 cross-talk and a CREB/PSAT1 axis as a driver of resistance to VEGFR2-TKIs in lung cancer, nominating ADRB2 blockade as a sensitizer.

    Evidence Co-IP of ADRB2/VEGFR2, propranolol treatment, CREB/PSAT1 analysis in NSCLC cells and xenografts

    PMID:35075132

    Open questions at the time
    • Direct vs. indirect nature of ADRB2/VEGFR2 interaction unresolved
    • Single lab characterization
  11. 2019 Medium

    Mapped the transcriptional output of cancer-cell ADRB2 activation to an ERK1/2-JNK-MAPK cascade engaging NF-κB, AP-1, CREB and STAT3, with receptor-subtype specificity.

    Evidence Subtype-specific pharmacology (ICI118,551 vs. atenolol), pathway analysis, xenograft stress model in gastric cancer

    PMID:31624248

    Open questions at the time
    • Relative contribution of each transcription factor not dissected
    • Effects on normal gastric epithelium untested
  12. 2019 Medium

    Established miR-15a-5p as a direct repressor of ADRB2 via its 3'UTR, defining a post-transcriptional brake that limits airway inflammatory gene expression.

    Evidence Luciferase reporter with WT/mutant 3'UTR, biotin pull-down, siRNA knockdown, ELISA in nasal epithelial cells

    PMID:31104300

    Open questions at the time
    • In vivo relevance of the miR-15a-5p/ADRB2 axis not tested
    • Whether miR-16 acts identically not shown here
  13. 2019 Medium

    Showed that environmental epigenetic silencing of ADRB2 by promoter hypermethylation impairs PI3K/Akt signaling and triggers cardiomyocyte apoptosis.

    Evidence Methylation chip/BSP, ADRB2 overexpression, LY294002 inhibition, TUNEL, rat instillation model

    PMID:30986742

    Open questions at the time
    • Enzymes driving the hypermethylation not identified
    • Single lab
  14. 2020 High

    Demonstrated that mesenchymal-cell ADRB2 promotes subchondral bone remodeling and osteoclastogenesis in joint osteoarthritis, extending its skeletal role to MSCs.

    Evidence Nestin-Cre x Adrb2 flox conditional knockout, crossbite model, histomorphometry and osteoclast quantification

    PMID:31926929

    Open questions at the time
    • Pro-osteoclastic mediators downstream of MSC ADRB2 not fully defined
    • Relationship to RANKL/OPG mechanism from PDLCs not directly linked
  15. 2022 High

    Identified the hepatokine ERAP1 and the deubiquitinase USP33 as opposing regulators of ADRB2 protein stability that gate insulin signaling in muscle.

    Evidence Reciprocal Co-IP of ERAP1-ADRB2, USP33 knockdown/overexpression, hepatic ERAP1 manipulation, insulin-sensitivity assays

    PMID:35192681

    Open questions at the time
    • Ubiquitin ligase opposing USP33 not identified
    • Site of ADRB2 ubiquitination unmapped
  16. 2022 Medium

    Linked ADRB2/PKA/CREB signaling to PPARγ-driven lipid synthesis, defining a role in glandular lipid production.

    Evidence Agonist/antagonist pharmacology, CREB phosphorylation and PPARγ/SREBP-1 readouts, lipid staining in meibomian gland cells

    PMID:36012741

    Open questions at the time
    • Whether CREB directly drives PPARγ transcription not shown
    • Single cell-type, single lab
  17. 2023 Medium

    Showed ADRB2 promotes fibroblast-to-myofibroblast differentiation by stabilizing SMAD2/3, with inhibition attenuating lung fibrosis.

    Evidence ADRB2 gain/loss in lung fibroblasts, pSMAD2/3 immunoblot, proteasome inhibition, bleomycin mouse model

    PMID:37923730

    Open questions at the time
    • How ADRB2 controls SMAD2/3 proteasomal degradation mechanistically unclear
    • Single lab
  18. 2023 Medium

    Found that ADRB2 activation by exercise can restore autophagy-lysosomal function via VMA21/V-ATPase to reduce amyloid pathology, an autophagy-promoting role contrasting its HCC autophagy-suppressing role.

    Evidence Exercise intervention and propranolol blockade in APP-PSEN1 mice, AMPK-mTOR/VMA21 analysis, amyloid and cognition readouts

    PMID:37964627

    Open questions at the time
    • Reconciliation with autophagy-suppressing role in cancer unresolved
    • Direct link from ADRB2 to VMA21 not mechanistically dissected
  19. 2024 Medium

    Defined ADRB2 as an inhibitory checkpoint on CAR-T cells acting through a ZAP-70/NF-κB axis, nominating its knockdown to enhance anti-tumor T-cell function.

    Evidence RNAi knockdown in CAR-T cells, cytotoxicity and activation/exhaustion marker profiling, ZAP-70/NF-κB analysis, prostate cancer xenografts

    PMID:39228124

    Open questions at the time
    • How ADRB2 couples to ZAP-70 not resolved
    • Endogenous catecholamine source in tumor not addressed
  20. 2025 High

    Placed ADRB2 in a neuroimmune circuit, showing ADRB2+ interstitial macrophages sense sympathetic norepinephrine to amplify lung inflammation during pneumonia.

    Evidence Opto/chemogenetic neural-circuit manipulation, norepinephrine measurement, ADRB2+ macrophage functional characterization, lethal pneumonia model

    PMID:40466637

    Open questions at the time
    • Intracellular signaling from ADRB2 to cytokine output in macrophages not detailed
    • Generalizability beyond severe pneumonia unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • How ADRB2 signaling is rerouted to opposite outcomes in different cell types—autophagy suppression vs. promotion, pro- vs. anti-inflammatory effects—remains unresolved at the level of cell-type-specific effector wiring.
  • No unifying account of context-dependent G-protein/effector coupling
  • Structural basis for allele- and cell-type-specific signaling unmapped
  • Endogenous ligand source and concentration in each tissue often inferred rather than measured

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060089 molecular transducer activity 3 GO:0098772 molecular function regulator activity 2
Localization
GO:0005886 plasma membrane 1
Pathway
R-HSA-162582 Signal Transduction 3 R-HSA-74160 Gene expression (Transcription) 3 R-HSA-168256 Immune System 2 R-HSA-392499 Metabolism of proteins 2 R-HSA-9612973 Autophagy 2
Partners
ERAP1HIC1PHD3USP33VEGFR2

Evidence

Reading pass · 20 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2016 ADRB2 signaling negatively regulates autophagy by disrupting the Beclin1/VPS34/Atg14 complex in an Akt-dependent manner, leading to HIF1α stabilization through inhibition of autophagic degradation, reprogramming of HCC cell glucose metabolism, and acquisition of sorafenib resistance. Knockdown of ADRB2 enhanced autophagy and destabilized HIF1α. Immunoblotting, immunofluorescence, immunoprecipitation, knockdown/inhibitor studies in HCC cell lines and nude mouse xenografts Journal of hepatology High 27154061
2011 HIC1 (Hypermethylated in Cancer 1) is a direct transcriptional repressor of ADRB2. Loss of HIC1 in breast cancer cells leads to upregulation of ADRB2, and agonist-mediated stimulation of ADRB2 increases migration and invasion of MDA-MB-231 cells; these effects are abolished by HIC1 re-expression or ADRB2 siRNA knockdown. Promoter luciferase assay, chromatin immunoprecipitation (ChIP), sequential ChIP, siRNA knockdown, migration/invasion assays The Journal of biological chemistry High 22194601
2014 Mechanical compressive force upregulates Adrb2 expression in human periodontal ligament cells (PDLCs) via elevation of intracellular Ca2+ concentration. Activation of Adrb2 in PDLCs increases the RANKL/OPG ratio and promotes peripheral blood mononuclear cell differentiation into osteoclasts, thereby facilitating bone resorption and orthodontic tooth movement. In vitro compressive force application to primary PDLCs, intracellular Ca2+ measurement, RANKL/OPG ratio assay, co-culture osteoclastogenesis assay, Adrb1/2 knockout mice, superior cervical ganglionectomy in rats Journal of dental research High 25252876
2017 α-Ketoglutarate (AKG) inhibits PHD3 expression and blocks PHD3-ADRB2 interaction, thereby increasing ADRB2 protein stability. AKG rescues skeletal muscle atrophy and protein degradation through this PHD3/ADRB2-mediated mechanism. Pharmacological and genetic approaches (PHD3 inhibition/knockdown), co-immunoprecipitation of PHD3-ADRB2, corticosterone-induced atrophy model, Duchenne muscular dystrophy mouse model FASEB journal Medium 28939592
2018 Pancreas-specific deletion of Adrb2 results in glucose intolerance and impaired insulin secretion specifically in female mice. Mechanistically, neonatal Adrb2 loss increases VEGF-A production in female neonatal β-cells, causing hyper-vascularized islets during development that disrupts insulin production and exocytosis. Neonatal VEGF-A receptor blockade fully rescues the glucose homeostasis deficits. Conditional knockout (nestin-Cre and pancreas-specific Cre x Adrb2 flox mice), glucose tolerance tests, insulin secretion assays, VEGF-A measurement, VEGFR blockade rescue experiments eLife High 30303066
2020 Conditional deletion of Adrb2 specifically in nestin+ mesenchymal stem cells attenuates subchondral bone loss and cartilage degradation in a temporomandibular joint osteoarthritis model, demonstrating that Adrb2 signaling in MSCs promotes osteoclastogenesis and subchondral bone remodeling. Nestin-Cre x Adrb2 flox conditional knockout mice, unilateral anterior crossbite model, histomorphometry, bone mineral density, osteoclast surface quantification, pro-osteoclastic factor expression Bone High 31926929
2022 ERAP1 (hepatokine endoplasmic reticulum aminopeptidase 1) physically interacts with ADRB2 and reduces ADRB2 protein expression by decreasing USP33 (ubiquitin-specific peptidase 33)-mediated deubiquitination, thereby interrupting ADRB2-stimulated insulin signaling in skeletal muscle. Co-immunoprecipitation of ERAP1-ADRB2 interaction, USP33 knockdown/overexpression, hepatic ERAP1 overexpression and knockdown in mice, insulin sensitivity assays Diabetes High 35192681
2010 ADRB2 haplotypes constructed from 26 polymorphisms across the entire intronless gene (promoter, 5'UTR, coding, 3'UTR) drive differential cell-surface β2AR protein expression and agonist-promoted downregulation in a haplotype-dependent manner when expressed in COS-7 cells. Whole-gene haplotype transfection into COS-7 cells, radioligand binding for cell-surface receptor quantification, agonist-promoted downregulation assays PloS one Medium 20686604
2022 Activation of the ADRB2/PKA signaling pathway enhances PPARγ expression and lipid synthesis in human meibomian gland epithelial cells (HMGECs). The ADRB2 agonist salbutamol increased PPARγ expression and lipid synthesis, while the ADRB2 antagonist timolol had the opposite effect, mediated through CREB phosphorylation. Pharmacological agonist/antagonist treatment of HMGECs, immunoblotting for CREB phosphorylation, PPARγ and SREBP-1 expression, LipidTOX staining, AdipoRed assay, Oil Red O staining International journal of molecular sciences Medium 36012741
2023 Aerobic exercise activates ADRB2/β2-adrenergic receptor signaling, which reverses autophagy-lysosomal deficits by upregulating VMA21 levels to restore V-ATPase function, reducing amyloid-β pathology in APP-PSEN1 mice. Propranolol (ADRB2 antagonist) blocked these exercise-induced benefits. Aerobic exercise intervention in APP-PSEN1 transgenic mice, propranolol pharmacologic blockade, AMPK-mTOR pathway analysis, VMA21 expression, amyloid-β quantification, cognitive testing Autophagy Medium 37964627
2019 PM2.5 exposure causes ADRB2 promoter hypermethylation, reducing β2AR expression and inhibiting PI3K/Akt signaling, which activates Bcl-2/BAX and p53 apoptotic pathways in cardiomyocytes. ADRB2 overexpression attenuated PM2.5-induced apoptosis, an effect abolished by PI3K inhibitor LY294002. DNA methylation chip and bisulfite sequencing PCR (BSP) in AC16 cardiomyocytes, ADRB2 overexpression transgenic cell lines, PI3K inhibitor LY294002, TUNEL assay, rat intratracheal instillation model, echocardiography Environment international Medium 30986742
2018 ADRB2 Gly16 allele carriers with heart failure show defective β2AR-coupled inhibitory Gi protein signaling in vitro, and Gly16 allele carriers show beneficial response to β-blocker therapy in a dose-dependent manner, whereas Arg16 homozygotes show no response. In vitro signaling assays for Gi coupling, multicenter cohort study (2403 + 919 patients), genotype-stratified analysis of clinical outcomes Cell discovery Medium 30374408
2018 ADRB2 signaling promotes resistance to VEGFR2-TKIs in non-small cell lung cancer via upregulation of ADRB2/VEGFR2 interaction and activation of the ADRB2/CREB/PSAT1 signaling pathway. Pharmacologic ADRB2 inhibition (propranolol) sensitized NSCLC cells to VEGFR2-TKIs in vitro and in vivo. Co-immunoprecipitation of ADRB2/VEGFR2 interaction, ADRB2 inhibitor (propranolol) treatment in NSCLC cell lines and xenograft models, CREB/PSAT1 pathway analysis Cell death discovery Medium 35075132
2019 ADRB2 activation by epinephrine/norepinephrine in gastric cancer cells promotes proliferation, invasion, and metastasis through the ERK1/2-JNK-MAPK pathway and transcription factors NF-κB, AP-1, CREB, and STAT3. ADRB2-specific antagonist ICI118,551 reversed these effects; ADRB1 antagonist atenolol had no effect. Proliferation, migration, invasion, cell cycle, and apoptosis assays in GC cell lines; ERK1/2-JNK-MAPK pathway analysis; xenograft mouse models with chronic restraint stress; ICI118,551 and atenolol pharmacologic discrimination Cell death & disease Medium 31624248
2019 miR-15a-5p directly targets the ADRB2 3'UTR and reduces ADRB2 mRNA and protein expression in a dose-dependent manner. ADRB2 knockdown inhibited IL-13-induced expression of GM-CSF, eotaxin, and MUC5AC in nasal epithelial cells, and miR-15a-5p mediated its anti-inflammatory effect through ADRB2. Luciferase reporter assay (wild-type vs. mutant ADRB2 3'UTR), biotin pull-down assay, siRNA knockdown, ELISA, Western blotting in IL-13-stimulated human nasal epithelial cells Human cell Medium 31104300
2025 A subpopulation of ADRB2+ interstitial macrophages surrounding pulmonary sympathetic nerves responds to norepinephrine released via a CeA-RVLM-sympathetic neural pathway, amplifying inflammatory cytokine production and lung injury during severe pneumonia. Specific inhibition of pulmonary sympathetic nerves or ADRB2 signaling improved outcomes. Optogenetic/chemogenetic inhibition of CeA GABAergic neurons, sympathetic nerve manipulation, norepinephrine measurement, ADRB2+ macrophage identification and functional characterization, lethal pneumonia mouse model Immunity High 40466637
2023 ADRB2 inhibition suppresses TGF-β1-induced fibroblast-to-myofibroblast differentiation by suppressing SMAD2/3 activation and increasing phospho-SMAD2/3 proteasome degradation. Conversely, ADRB2 enhancement induces fibroblast-to-myofibroblast differentiation. ADRB2 inhibition attenuated bleomycin-induced lung fibrosis in vivo. ADRB2 knockdown/overexpression in lung fibroblasts, pSMAD2/3 immunoblotting, proteasome inhibitor experiments, bleomycin mouse model Cell death discovery Medium 37923730
2012 A functional SNP upstream of ADRB2 (rs34623097-A) reduces transcriptional activity of the ADRB2 promoter by approximately 10% and modulates nuclear factor binding affinity. The A allele was associated with increased obesity risk in Oceanic populations, consistent with reduced ADRB2 expression. Luciferase reporter assay comparing rs34623097-A vs. G allele, electrophoretic mobility shift assay (EMSA) for nuclear factor binding International journal of obesity Medium 23229733
2018 A functional SNP upstream of ADRB2 (rs12654778) reduces relative ADRB2 promoter activity by ~26% (A vs. G allele) and modulates binding affinity of transcription factor neurofibromin 1 (NF1), establishing an allele-specific transcriptional regulatory mechanism linked to COPD susceptibility. Luciferase reporter assay, chromatin immunoprecipitation (ChIP) for NF1 binding, real-time PCR of ADRB2 expression in COPD patients vs. controls International journal of chronic obstructive pulmonary disease Medium 29588580
2024 ADRB2 functions as an inhibitory checkpoint receptor on CAR-T cells. ADRB2 knockdown in CAR-T cells enhanced cytotoxicity against prostate cancer cells, increased CD69, CD107a, GzmB, IFN-γ, T-bet, and GLUT-1, improved proliferation, reduced apoptosis, and increased Bcl-2. The ZAP-70/NF-κB signaling axis was responsible for the improved functions. shβ2-CAR-T cells outperformed conventional CAR-T cells in vivo. RNAi knockdown of ADRB2 in CAR-T cells, cytotoxicity assays, flow cytometry for activation/exhaustion markers, ZAP-70/NF-κB pathway analysis, xenograft prostate cancer mouse model Molecular therapy Medium 39228124

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2019 Chronic stress promotes gastric cancer progression and metastasis: an essential role for ADRB2. Cell death & disease 200 31624248
2016 ADRB2 signaling promotes HCC progression and sorafenib resistance by inhibiting autophagic degradation of HIF1α. Journal of hepatology 199 27154061
2007 Effect of ADRB2 polymorphisms on response to longacting beta2-agonist therapy: a pharmacogenetic analysis of two randomised studies. Lancet (London, England) 167 18156033
1998 Association of persistent bronchial hyperresponsiveness with beta2-adrenoceptor (ADRB2) haplotypes. A population study. American journal of respiratory and critical care medicine 101 9847294
2014 Effect of rare variants in ADRB2 on risk of severe exacerbations and symptom control during longacting β agonist treatment in a multiethnic asthma population: a genetic study. The Lancet. Respiratory medicine 82 24621682
2019 PM2.5-induced ADRB2 hypermethylation contributed to cardiac dysfunction through cardiomyocytes apoptosis via PI3K/Akt pathway. Environment international 71 30986742
2004 Polymorphisms of IL4, IL13, and ADRB2 genes in COPD. Chest 71 15596681
2014 Interaction of the ADRB2 gene polymorphism with childhood trauma in predicting adult symptoms of posttraumatic stress disorder. JAMA psychiatry 70 25162199
2014 Force-induced Adrb2 in periodontal ligament cells promotes tooth movement. Journal of dental research 64 25252876
2002 Polymorphisms of the beta2 -adrenoceptor (ADRB2) gene and essential hypertension: the ECTIM and PEGASE studies. Journal of hypertension 58 11821707
2000 Polymorphisms of the beta2-adrenergic receptor gene (ADRB2) in relation to cardiovascular risk factors in men. Journal of internal medicine 48 10971791
2012 An environmental epigenetic study of ADRB2 5'-UTR methylation and childhood asthma severity. Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology 47 22862293
2009 Polymorphism of the ADRB2 gene and response to inhaled beta- agonists in children with asthma: a meta-analysis. The Journal of asthma : official journal of the Association for the Care of Asthma 46 19905915
2017 α-Ketoglutarate prevents skeletal muscle protein degradation and muscle atrophy through PHD3/ADRB2 pathway. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 45 28939592
2010 Combined pharmacogenetic effect of ADCY9 and ADRB2 gene polymorphisms on the bronchodilator response to inhaled combination therapy. Journal of clinical pharmacy and therapeutics 44 21545619
2008 Genetic variation in candidate obesity genes ADRB2, ADRB3, GHRL, HSD11B1, IRS1, IRS2, and SHC1 and risk for breast cancer in the Cancer Prevention Study II. Breast cancer research : BCR 43 18611262
2013 Effect of ADRB2 polymorphisms on the efficacy of salmeterol and tiotropium in preventing COPD exacerbations: a prespecified substudy of the POET-COPD trial. The Lancet. Respiratory medicine 38 24461901
2010 Common ADRB2 haplotypes derived from 26 polymorphic sites direct beta2-adrenergic receptor expression and regulation phenotypes. PloS one 36 20686604
2019 ADRB2-Targeting Therapies for Prostate Cancer. Cancers 34 30871232
2004 ADRB2 polymorphisms and asthma susceptibility: transmission disequilibrium test and meta-analysis. International archives of allergy and immunology 32 15153795
2006 Association of a beta-2 adrenoceptor (ADRB2) gene variant with a blunted in vivo lipolysis and fat oxidation. International journal of obesity (2005) 31 17130852
2012 Polymorphisms in ADRB2 gene can modulate the response to bronchodilators and the severity of cystic fibrosis. BMC pulmonary medicine 30 22950544
2008 Lung function response to 12-week treatment with combined inhalation of long-acting beta2 agonist and glucocorticoid according to ADRB2 polymorphism in patients with chronic obstructive pulmonary disease. Lung 30 18758858
2018 β‑blockers inhibit the viability of breast cancer cells by regulating the ERK/COX‑2 signaling pathway and the drug response is affected by ADRB2 single‑nucleotide polymorphisms. Oncology reports 29 30542705
2012 Human-specific SNP in obesity genes, adrenergic receptor beta2 (ADRB2), Beta3 (ADRB3), and PPAR γ2 (PPARG), during primate evolution. PloS one 28 22937051
2023 Aerobic exercise attenuates autophagy-lysosomal flux deficits by ADRB2/β2-adrenergic receptor-mediated V-ATPase assembly factor VMA21 signaling in APP-PSEN1/PS1 mice. Autophagy 27 37964627
2020 Conditional deletion of Adrb2 in mesenchymal stem cells attenuates osteoarthritis-like defects in temporomandibular joint. Bone 27 31926929
2020 HSP90AA1, ADRB2, TBL1XR1 and HSPB1 are chronic obstructive pulmonary disease-related genes that facilitate squamous cell lung cancer progression. Oncology letters 27 32194709
2017 Differential lipid metabolism outcomes associated with ADRB2 gene polymorphisms in response to two dietary interventions in overweight/obese subjects. Nutrition, metabolism, and cardiovascular diseases : NMCD 27 29331538
2013 Association of the FTO and ADRB2 genes with body composition and fat distribution in obese women. Maturitas 27 23911093
2011 Loss of Hypermethylated in Cancer 1 (HIC1) in breast cancer cells contributes to stress-induced migration and invasion through β-2 adrenergic receptor (ADRB2) misregulation. The Journal of biological chemistry 27 22194601
2008 Intraocular pressure response to topical beta-blockers associated with an ADRB2 single-nucleotide polymorphism. Archives of ophthalmology (Chicago, Ill. : 1960) 27 18625943
2022 Cardamonin suppressed the migration, invasion, epithelial mesenchymal transition (EMT) and lung metastasis of colorectal cancer cells by down-regulating ADRB2 expression. Pharmaceutical biology 26 35645356
2018 Adrb2 controls glucose homeostasis by developmental regulation of pancreatic islet vasculature. eLife 26 30303066
2018 ADRB2 polymorphism Arg16Gly modifies the natural outcome of heart failure and dictates therapeutic response to β-blockers in patients with heart failure. Cell discovery 25 30374408
2014 Beta-2 adrenergic receptor (ADRB2) gene polymorphisms and the risk of asthma: a meta-analysis of case-control studies. PloS one 25 25111792
2006 Molecular-based haplotype analysis of the beta 2-adrenergic receptor gene (ADRB2) in Japanese asthmatic and non-asthmatic subjects. Allergology international : official journal of the Japanese Society of Allergology 25 17075257
2019 ADRB2 suppresses IL-13-induced allergic rhinitis inflammatory cytokine regulated by miR-15a-5p. Human cell 24 31104300
2012 ADRB2 polymorphisms and budesonide/formoterol responses in COPD. Chest 24 22383665
2011 ADRB2 Gly16Arg polymorphism, asthma control and lung function decline. The European respiratory journal 24 21436355
2008 CT scanning-based phenotypes vary with ADRB2 polymorphisms in chronic obstructive pulmonary disease. Respiratory medicine 24 18789663
2023 Saikosaponin D reverses epinephrine- and norepinephrine-induced gemcitabine resistance in intrahepatic cholangiocarcinoma by downregulating ADRB2/glycolysis signaling. Acta biochimica et biophysica Sinica 23 37489008
2005 Beta-2 adrenergic receptor gene (ADRB2) polymorphism and risk for lung adenocarcinoma: a case-control study in a Chinese population. Cancer letters 23 16289313
2024 Intrinsic ADRB2 inhibition improves CAR-T cell therapy efficacy against prostate cancer. Molecular therapy : the journal of the American Society of Gene Therapy 20 39228124
2015 Four-locus gene interaction between IL13, IL4, FCER1B, and ADRB2 for asthma in Chinese Han children. Pediatric pulmonology 20 26613553
2013 Genetic variation in the beta-2 adrenergic receptor (ADRB2) predicts functional gastrointestinal diagnoses and poorer health-related quality of life. Alimentary pharmacology & therapeutics 20 23786226
2025 A brain-to-lung signal from GABAergic neurons to ADRB2+ interstitial macrophages promotes pulmonary inflammatory responses. Immunity 19 40466637
2019 Association of ADRB2 rs1042713 with Obesity and Obesity-Related Phenotypes and Its Interaction with Dietary Fat in Modulating Glycaemic Indices in Malaysian Adults. Journal of nutrition and metabolism 19 31007954
2013 Obesity-related gene ADRB2, ADRB3 and GHRL polymorphisms and the response to a weight loss diet intervention in adult women. Genetics and molecular biology 19 24688286
2010 Polymorphisms in the ACE and ADRB2 genes and risks of aging-associated phenotypes: the case of myocardial infarction. Rejuvenation research 19 20230274
2010 ADRB2 haplotype is associated with glucose tolerance and insulin sensitivity in obese postmenopausal women. Obesity (Silver Spring, Md.) 19 20829805
2022 Targeting ADRB2 enhances sensitivity of non-small cell lung cancer to VEGFR2 tyrosine kinase inhibitors. Cell death discovery 18 35075132
2021 The role of ADRB2 gene polymorphisms in malignancies. Molecular biology reports 18 33675465
2015 Expression of the beta-2 adrenergic receptor (ADRB-2) in human and monkey ovarian follicles: a marker of growing follicles? Journal of ovarian research 18 25824473
2006 Impact of variation in ADRB2, ADRB3, and GNB3 genes on body mass index and waist circumference in a Brazilian population. American journal of human biology : the official journal of the Human Biology Council 18 16493638
2002 Determination of beta2-adrenergic receptor (ADRB2) haplotypes by a multiplexed polymerase chain reaction assay. Human mutation 18 12442282
2022 Hepatokine ERAP1 Disturbs Skeletal Muscle Insulin Sensitivity Via Inhibiting USP33-Mediated ADRB2 Deubiquitination. Diabetes 17 35192681
2019 Evaluation of genetic risk related to catechol-O-methyltransferase (COMT) and β2-adrenergic receptor (ADRB2) activity in different diagnostic subgroups of temporomandibular disorder in Brazilian patients. International journal of oral and maxillofacial surgery 17 31285095
2017 Variants of the ADRB2 Gene in COPD: Systematic Review and Meta-Analyses of Disease Risk and Treatment Response. COPD 17 28506092
2009 Development of novel microarray methodology for the study of mutations in the SERPINA1 and ADRB2 genes--their association with Obstructive Pulmonary Disease and Disseminated Bronchiectasis in Greek patients. Clinical biochemistry 17 19747908
2023 ADRB2 inhibition combined with antioxidant treatment alleviates lung fibrosis by attenuating TGFβ/SMAD signaling in lung fibroblasts. Cell death discovery 16 37923730
2019 Upregulation of microRNA‑16 alters the response to inhaled β‑agonists in patients with asthma though modulating expression of ADRB2. Molecular medicine reports 16 30942450
2013 Single nucleotide polymorphisms of ADRB2 gene and their association with susceptibility for Plasmodium falciparum malaria and asthma in an Indian population. Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases 16 24012958
2011 ADRB2 and LEPR gene polymorphisms: synergistic effects on the risk of obesity in Japanese. Obesity (Silver Spring, Md.) 16 21233812
2009 No consistent effect of ADRB2 haplotypes on obesity, hypertension and quantitative traits of body fatness and blood pressure among 6,514 adult Danes. PloS one 16 19779622
2019 Polymorphisms in COMT, ADRB2 and HTR1A genes are associated with temporomandibular disorders in individuals with other arthralgias. Cranio : the journal of craniomandibular practice 15 31264537
2019 Association between ADRB2, IL33, and IL2RB gene polymorphisms and lung cancer risk in a Chinese Han population. International immunopharmacology 15 31685439
2010 A46G and C79G polymorphisms in the β2-adrenergic receptor gene (ADRB2) and essential hypertension risk: a meta-analysis. Hypertension research : official journal of the Japanese Society of Hypertension 15 20739939
2009 Polymorphisms in the ADRB2 gene and Graves disease: a case-control study and a meta-analysis of available evidence. BMC medical genetics 15 19284637
2022 Activation of ADRB2/PKA Signaling Pathway Facilitates Lipid Synthesis in Meibocytes, and Beta-Blocker Glaucoma Drug Impedes PKA-Induced Lipid Synthesis by Inhibiting ADRB2. International journal of molecular sciences 14 36012741
2022 ADRB2 expression predicts the clinical outcomes and is associated with immune cells infiltration in lung adenocarcinoma. Scientific reports 14 36163241
2021 ADRB2 is a potential protective gene in breast cancer by regulating tumor immune microenvironment. Translational cancer research 14 35116377
2019 β2-Adrenergic Receptor (ADRB2) Gene Polymorphisms and Risk of COPD Exacerbations: The Rotterdam Study. Journal of clinical medicine 14 31683975
2012 Effect of β2-adrenergic receptor gene (ADRB2) 3' untranslated region polymorphisms on inhaled corticosteroid/long-acting β2-adrenergic agonist response. Respiratory research 14 22559839
2012 CYP2J2 -50 G/T and ADRB2 G46A gene polymorphisms in Saudi subjects with hypertension. Genetic testing and molecular biomarkers 14 22731644
2009 Characterization of a de novo translocation t(5;18)(q33.1;q12.1) in an autistic boy identifies a breakpoint close to SH3TC2, ADRB2, and HTR4 on 5q, and within the desmocollin gene cluster on 18q. American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics 14 19086034
2019 Role of THRB, ARG1, and ADRB2 Genetic Variants on Bronchodilators Response in Asthmatic Children. Journal of aerosol medicine and pulmonary drug delivery 13 30855197
2018 A functional SNP upstream of the ADRB2 gene is associated with COPD. International journal of chronic obstructive pulmonary disease 13 29588580
2015 Effect of ADRB2 (adrenergic receptor β2) gene polymorphisms on the occurrence of asthma and on the response to nebulized salbutamol in South Indian patients with bronchial asthma. The Journal of asthma : official journal of the Association for the Care of Asthma 13 25985706
2015 Influence of ADRB2 Gln27Glu and ADRB3 Trp64Arg polymorphisms on body weight and body composition changes after a controlled weight-loss intervention. Applied physiology, nutrition, and metabolism = Physiologie appliquee, nutrition et metabolisme 13 26888112
2009 Role of ADRB2 gene polymorphism in asthma and response to beta(2)-agonists in Polish children. Journal of applied genetics 13 19638684
2024 CRISPR-CasRx-mediated disruption of Aqp1/Adrb2/Rock1/Rock2 genes reduces intraocular pressure and retinal ganglion cell damage in mice. Nature communications 12 39080269
2015 Association of the ADRB2 (rs2053044) polymorphism and angiotensin-converting enzyme-inhibitor blood pressure response in the African American Study of Kidney Disease and Hypertension. Pharmacogenetics and genomics 12 26111150
2014 SPINK5 and ADRB2 haplotypes are risk factors for asthma in Mexican pediatric patients. The Journal of asthma : official journal of the Association for the Care of Asthma 12 25233048
2011 A pharmacogenetic study of ADRB2 polymorphisms and indacaterol response in COPD patients. The pharmacogenomics journal 12 22158330
2007 ADRB2 Arg16Gly polymorphism, lung function, and mortality: results from the Atherosclerosis Risk in Communities study. PloS one 12 17356698
2022 FTO and ADRB2 Genetic Polymorphisms Are Risk Factors for Earlier Excessive Gestational Weight Gain in Pregnant Women with Pregestational Diabetes Mellitus: Results of a Randomized Nutrigenetic Trial. Nutrients 11 35268025
2015 ADRB2 polymorphisms predict the risk of myocardial infarction and coronary artery disease. Genetics and molecular biology 11 26692153
2012 ADRB2 G-G haplotype associated with breast cancer risk among Hispanic and non-Hispanic white women: interaction with type 2 diabetes and obesity. Cancer causes & control : CCC 11 22864926
2006 Anger suppression and adiposity modulate association between ADRB2 haplotype and cardiovascular stress reactivity. Psychosomatic medicine 11 16554384
2005 Polymorphic variants of the beta2-adrenergic receptor (ADRB2) gene and ADRB2-related propanolol-induced dyslipidemia in the Colombian population. Methods and findings in experimental and clinical pharmacology 11 16082424
2023 10-Gingerol Enhances the Effect of Taxol in Triple-Negative Breast Cancer via Targeting ADRB2 Signaling. Drug design, development and therapy 10 36712945
2020 The Combined Effect of Polygenic Risk from FTO and ADRB2 Gene Variants, Odds of Obesity, and Post-Hipcref Diet Differences. Lifestyle genomics 10 32101872
2013 Interactions between social/ behavioral factors and ADRB2 genotypes may be associated with health at advanced ages in China. BMC geriatrics 10 24016068
2012 A functional SNP upstream of the beta-2 adrenergic receptor gene (ADRB2) is associated with obesity in Oceanic populations. International journal of obesity (2005) 10 23229733
2007 Association between polymorphisms of ACE, B2AR, ANP and ENOS and cardiovascular diseases: a community-based study in the Matsu area. Clinical chemistry and laboratory medicine 10 17243909
2002 Allele and genotype frequencies of polymorphic DCP1, CETP, ADRB2, and HTR2A in the Egyptian population. European journal of clinical pharmacology 10 11956670
2024 Genetic variants in DBC1, SIRT1, UCP2 and ADRB2 as potential biomarkers for severe obesity and metabolic complications. Frontiers in genetics 9 38841722
2021 ADRB2 haplotypes and asthma exacerbations in children and young adults: An individual participant data meta-analysis. Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology 9 34128573
2015 ADRB2 polymorphisms in allergic asthma in Han Chinese children. International forum of allergy & rhinology 9 26633084

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