Affinage

CCKBR

Gastrin/cholecystokinin type B receptor · UniProt P32239

Length
447 aa
Mass
48.4 kDa
Annotated
2026-06-09
57 papers in source corpus 20 papers cited in narrative 21 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 5/6 claims corpus-supported (83%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CCKBR (CCK2R) is a gastrin/CCK-responsive G-protein-coupled receptor that couples to Gs, Gq, and Gi to drive proliferative, secretory, and neuromodulatory programs, with distinct receptor conformations dictating G-protein bias (PMID:41270732). Through a Gαq-dependent mechanism requiring the conserved NPXXY motif, CCKBR activates JAK2/STAT3 to promote cell proliferation (PMID:15640156), and it additionally engages ERK and PI3K/AKT signaling that supports tumor cell growth, migration, and angiogenesis—activities amplified by gain-of-function somatic mutations found in colorectal and gastric cancers (PMID:22516348, PMID:22786615). Agonist-occupied CCKBR also recruits β-arrestin1/2, which mediates receptor endocytosis and, in colonic epithelium, suppresses BMP2 transcription to promote symmetric cancer stem-cell division (PMID:23891976, PMID:33042258). In the gastrointestinal tract, CCKBR marks Lgr5neg/low antral +4 stem cells and ECL-cell isthmus progenitors, and gastrin/progastrin signaling through CCKBR-dependent ERK activation drives stem-cell expansion, ECL-cell hyperplasia, and carcinogenesis (PMID:24951258, PMID:32330731). CCKBR also governs intestinal and renal transport physiology: in intestinal epithelium it inhibits NHE3 via PKC/NHERF1/NHERF2 to limit sodium absorption and protect against salt-sensitive hypertension, and it restrains glucose handling through PI3K/Akt/eIF4B and Erk/NF-κB pathways (PMID:35674015, PMID:39950948, PMID:39721589). In the CNS, CCKBR is required for cortical development and for circuit-level synaptic plasticity, where Gαq/11-Ca2+ and Gαs-cAMP signaling (but not β-arrestin signaling) underlies long-term potentiation and associative memory (PMID:41360797, PMID:25875176, PMID:41888094).

Mechanistic history

Synthesis pass · year-by-year structured walk · 18 steps
  1. 2005 High

    Establishing how CCKBR transduces a proliferative signal, this work showed the receptor activates JAK2/STAT3 through Gαq and the conserved NPXXY motif, linking receptor architecture to a defined kinase cascade.

    Evidence Constitutively active Gαq transfection, Gαq–JAK2 co-IP, NPXXY mutagenesis, and transgenic Elas-CCK2 mouse pancreas

    PMID:15640156

    Open questions at the time
    • Did not resolve how Gαq physically couples to JAK2
    • Relevance of JAK2/STAT3 across other CCKBR-expressing tissues not addressed
  2. 2005 Low

    To map the ligand-binding mode, an extracellular receptor fragment was shown to bind CCK8 in the micromolar range, providing early biochemical evidence for the agonist contact region.

    Evidence Fluorescence titration of the CCK(B)-R(352-379) peptide with CCK8 in membrane-mimetic solvent

    PMID:15666329

    Open questions at the time
    • Used a receptor fragment rather than the full receptor
    • Single in vitro binding assay without functional correlate
  3. 2007 Medium

    Addressing how CCKBR expression is controlled, this work defined the SP1/C/EBP/GATA promoter requirements and a gastrin-driven PKC/MEK feed-forward loop regulating receptor transcription.

    Evidence Luciferase promoter-reporter mutagenesis, qPCR, PKC/MEK inhibition, and a gastric cryoulcer injury model

    PMID:17933865

    Open questions at the time
    • Functional consequence of myofibroblast CCKBR induction not defined
    • Direct factor binding to promoter sites inferred from mutagenesis only
  4. 2012 Medium

    To clarify CCKBR's contribution to tumorigenesis, somatic mutations from colorectal and gastric cancers were shown to be activating, increasing downstream signaling, migration, and angiogenesis.

    Evidence Functional receptor activity, migration, and angiogenesis assays on six mutant CCK2R variants in cancer cell lines

    PMID:22516348

    Open questions at the time
    • Which specific G-protein/effector pathway each mutation biases not resolved
    • In vivo tumorigenicity of mutants not tested
  5. 2012 Medium

    Demonstrating CCKBR signaling in a non-classical tumor type, gastrin stimulation in GIST xenografts hyperactivated KIT, PKC-θ, and PI3K-AKT and doubled tumor volume.

    Evidence GIST xenograft mouse model with gastrin, western blot, and Ki-67/mitotic IHC

    PMID:22786615

    Open questions at the time
    • Mechanistic link between CCKBR and KIT activation not dissected
    • No CCKBR loss-of-function control
  6. 2013 High

    Defining a β-arrestin-dependent transcriptional output, progastrin/CCKBR signaling was shown to suppress BMP2 via β-arrestin1/2, reducing Smad1/5/8 phosphorylation and ID4 to drive symmetric cancer stem-cell division.

    Evidence Microarray, β-arrestin1/2 siRNA, CCK2R-knockout crypt cultures, progastrin binding, and symmetric division markers

    PMID:23891976

    Open questions at the time
    • How β-arrestin represses BMP2 transcription not resolved
    • Stem-cell identity markers correlative
  7. 2013 Medium

    Connecting CCKBR to microRNA control in pancreatic cancer, miR-148a was shown to directly target the CCKBR 3'UTR to regulate proliferation and apoptosis.

    Evidence Luciferase 3'UTR reporter, western blot, and proliferation/apoptosis assays in PANC-1 and AsPC-1 cells

    PMID:23975374

    Open questions at the time
    • Downstream CCKBR effectors mediating the phenotype not fully mapped
    • Single lab
  8. 2014 High

    Resolving which gastric epithelial population CCKBR marks, the receptor was shown to label Lgr5neg/low +4 antral stem cells that progastrin interconverts and expands toward carcinogenesis.

    Evidence CCK2R-CreERT lineage tracing, organoid culture, genetic ablation, pharmacological inhibition, and MNU carcinogenesis

    PMID:24951258

    Open questions at the time
    • Signaling pathway driving interconversion not defined here
    • Human relevance of +4 population not established
  9. 2015 Medium

    Establishing a developmental role, dual deletion of CCKAR and CCKBR produced synergistic cortical patterning, corpus callosum, and interneuron migration defects.

    Evidence Compound double-knockout mice with embryonic neocortex transcriptomics and histology

    PMID:25875176

    Open questions at the time
    • CCKBR-specific contribution not separated from CCKAR
    • Cell-autonomous mechanism unresolved
  10. 2016 Medium

    Extending miR-148a regulation to gastric cancer, CCKBR was confirmed as a direct target whose knockdown phenocopies miR-148a anti-oncogenic effects via reduced STAT3/Akt activation.

    Evidence Luciferase 3'UTR reporter, siRNA phenocopy, proliferation/migration assays, and xenograft

    PMID:27518872

    Open questions at the time
    • Other miR-148a targets may contribute
    • Single lab
  11. 2020 High

    Identifying the ECL-cell hyperplasia origin, CCK2R+ isthmus progenitors were shown to expand under hypergastrinemia via CCKBR-driven ERK signaling, blocked by MEK inhibition.

    Evidence Cck2r-CreERT2 and Hdc-CreERT2 lineage tracing, gastrin/omeprazole infusion, organoids, and U0126

    PMID:32330731

    Open questions at the time
    • Upstream coupling of CCKBR to ERK in this niche not detailed
    • Reversibility of hyperplasia not addressed
  12. 2020 Medium

    Revealing a regulator of receptor abundance relevant to radiotheranostics, mTORC1 inhibition was shown to raise CCKBR protein and enhance β-arrestin1/2 recruitment, ERK phosphorylation, and minigastrin internalization in vivo.

    Evidence Kinase inhibitor screen, western blot, β-arrestin/ERK assays, and CCKBR xenograft SPECT/CT biodistribution

    PMID:33042258

    Open questions at the time
    • Mechanism by which mTORC1 controls CCKBR levels unresolved
    • Single lab
  13. 2022 High

    Defining a transport-regulatory function, intestinal CCKBR was shown to inhibit NHE3 through PKC-mediated NHERF1/NHERF2 to limit sodium absorption and protect against salt-sensitive hypertension.

    Evidence Intestinal-specific Cckbr knockout mice, Dahl salt-sensitive rats, sodium transport assays, and gastrin-SiO2 microsphere rescue

    PMID:35674015

    Open questions at the time
    • Direct CCKBR–NHERF physical coupling not structurally defined
    • Human translation limited
  14. 2024 Medium

    Extending CCKBR transport control to the kidney, renal tubular CCKBR was shown to inhibit SGLT2-mediated glucose reabsorption via Erk/NF-κB, with knockout increasing diabetes susceptibility.

    Evidence Renal tubule-specific Cckbr knockout mice, HFD/STZ model, and HK-2 high-glucose assays with pathway western blot

    PMID:39721589

    Open questions at the time
    • Direct mechanism linking CCKBR to SGLT2 downregulation not resolved
    • Single lab
  15. 2025 High

    Providing the structural basis of CCKBR signaling bias, cryo-EM of CCK8s-bound receptor with Gs, Gq, and Gi revealed conformation-encoded G-protein selectivity and enabled biased agonists, with Gs/Gq signaling shown beneficial in an Alzheimer's model.

    Evidence Cryo-EM at three G-protein subtypes, biased agonist pharmacology, 5×FAD mice, LTP, and western blot

    PMID:41270732

    Open questions at the time
    • Endogenous determinants of bias selection in vivo unknown
    • Downstream ADAM10/PLCB4 regulation not mechanistically dissected
  16. 2025 High

    Dissecting which signaling arm supports synaptic plasticity, a β-arrestin-biased agonist showed CCKBR-dependent LTP requires Gαq/11-Ca2+ and Gαs-cAMP, while β-arrestin signaling drives endocytosis and blocks potentiation.

    Evidence β-arrestin recruitment, MEA, Ca2+ and cAMP assays, endocytosis imaging, and fear memory behavior

    PMID:41360797

    Open questions at the time
    • Neuronal G-protein vs arrestin balance under physiological CCK release not measured
    • Circuit specificity not addressed
  17. 2025 Medium

    Extending CCKBR's metabolic role, intestinal CCKBR was shown to reduce glucose absorption by downregulating SGLT1/GLUT2 and stimulating incretin secretion via PI3K/Akt/eIF4B.

    Evidence Intestinal-specific Cckbr knockout mice, HFD model, OGTT, pathway analysis, human duodenal tissue, and gastrin-SiO2 microspheres

    PMID:39950948

    Open questions at the time
    • Direct CCKBR-to-transporter regulatory link not resolved
    • Single lab
  18. 2026 Medium

    Placing CCKBR in a reward circuit, CCK2R in BLA glutamatergic neurons was shown to be required for methamphetamine conditioned place preference and the associated synaptic remodeling in the VTA→BLA→BNST pathway.

    Evidence Cell-type-specific Cck knockout, optogenetics, chemogenetics, electrophysiology, and Golgi spine analysis

    PMID:41888094

    Open questions at the time
    • Receptor-proximal signaling in BLA neurons not defined
    • Single lab

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the structurally defined conformational basis of G-protein bias is selected physiologically across CCKBR's diverse tissues—and how the same receptor partitions between proliferative, transport-regulatory, and synaptic outputs—remains unresolved.
  • No unifying model of tissue-specific effector selection
  • Endogenous determinants of Gs/Gq/Gi/arrestin partitioning unknown
  • In vivo structural state of the receptor not captured

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 3
Pathway
R-HSA-112316 Neuronal System 3 R-HSA-162582 Signal Transduction 3 R-HSA-1643685 Disease 3 R-HSA-382551 Transport of small molecules 3
Partners
ARRB1ARRB2GNAQGNASJAK2NHERF1NHERF2

Evidence

Reading pass · 21 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2025 Cryo-EM structures of CCKBR in complex with the endogenous agonist sulfated CCK8 (CCK8s) and three different G protein subtypes (Gs, Gq, Gi) revealed that distinct receptor conformations contribute to selective G protein bias. Leveraging structural insights, synthetic biased agonists were developed: a Gi-biased agonist (z-44) and a Gq-biased agonist (3r1). CCKBR-Gs and -Gq signaling (but not -Gi) were found beneficial for Alzheimer's disease treatment; 3r1 ameliorated cognitive decline in 5×FAD mice, reduced amyloid-β plaques, and promoted LTP via upregulation of ADAM10 and PLCB4. Cryo-EM structure determination, biased agonist pharmacology, murine AD model (5×FAD), LTP assay, western blot Cell High 41270732
2025 A β-arrestin-biased CCKBR agonist (MF-8, IC50 = 0.9 nM) was discovered. Activation of CCKBR with MF-8 failed to induce neocortical long-term potentiation but efficiently induced CCKBR endocytosis. Multi-Electrode Array experiments demonstrated that CCKBR-dependent LTP requires Gαq/11-Ca2+ and Gαs-cAMP signaling pathways, and MF-8 completely blocked the potentiation through β-arrestin signaling. MF-8 also inhibited cue-to-cue associative fear memory formation in vivo. β-arrestin recruitment assay, multi-electrode array (MEA), calcium signaling assay, cAMP assay, fear memory behavioral test, CCKBR endocytosis imaging Nature communications High 41360797
2005 CCK2R activates JAK2 through a Gαq-dependent mechanism involving the conserved NPXXY motif in the receptor. Constitutively active Gαq (Q209L) associates with and activates JAK2 in transfected COS-7 cells. In pancreatic tumor cells expressing endogenous CCK2R, this leads to JAK2/STAT3 pathway activation, which contributes to CCK2R-mediated proliferation. In vivo, targeted CCK2R expression in Elas-CCK2 mouse pancreas activates JAK2 and STAT3. Constitutively active Gαq transfection, Co-IP (Gαq–JAK2 association), NPXXY motif mutagenesis, western blot (JAK2/STAT3 phosphorylation), transgenic mouse model The Journal of biological chemistry High 15640156
2013 Progastrin stimulates colonic cell proliferation via CCK2R and β-arrestin 1/2-dependent suppression of BMP2 transcription, leading to decreased Smad1/5/8 phosphorylation and suppression of ID4. This promotes symmetric division of putative cancer stem cells (increased CD44+, BrdU+, NUMB+ cells). CCK2R was necessary and sufficient for progastrin binding and induction of proliferation in human cancer cell lines; effects were blocked by recombinant BMP2. Microarray, siRNA knockdown (β-arrestin 1/2), CCK2R-knockout mouse colonic crypt cultures, progastrin binding assay, symmetric division analysis (CD44/BrdU/NUMB staining) Gastroenterology High 23891976
2014 CCK2R marks +4 antral stem cells (Lgr5neg/low) distinct from typical Lgr5high stem cells. Progastrin treatment interconverts Lgr5neg/low CCK2R+ cells into Lgr5high cells, increases CCK2R+ cell numbers, and promotes gland fission and MNU-induced carcinogenesis. Pharmacological inhibition or genetic ablation of CCK2R attenuated progastrin-dependent stem cell expansion and carcinogenesis. CCK2R-CreERT inducible lineage tracing, 3D organoid culture, CCK2R genetic ablation, CCK2R pharmacological inhibition, MNU carcinogenesis model Gut High 24951258
2020 Hypergastrinemia expands ECL cells primarily from CCK2R+ isthmus progenitors (not from mature Hdc+ ECL cells). Gastrin activates ERK signaling in vivo and in vitro via CCK2R; MEK1 inhibitor U0126 blocked hypergastrinemia-mediated ECL cell hyperplasia, sphere formation, and chromogranin A expression in CCK2R-derived organoids. Cck2r-CreERT2 lineage tracing, Hdc-CreERT2 lineage tracing, omeprazole/gastrin infusion models, 3D organoid/sphere formation, U0126 MEK inhibitor treatment, in vivo ERK phosphorylation assay Cellular and molecular gastroenterology and hepatology High 32330731
2022 Intestinal gastrin/CCKBR inhibits NHE3 (Na+/H+ exchanger 3) trafficking and activity through a PKC-mediated activation of NHERF1 and NHERF2, reducing intestinal sodium absorption. Intestinal epithelial cell-specific Cckbr knockout (Cckbrfl/fl villin-Cre) mice showed increased intestinal Na+ absorption and salt-sensitive hypertension. Gastrin-SiO2 microspheres (acting locally on intestinal CCKBR) prevented high-salt-induced hypertension. Intestinal-specific Cckbr knockout mice, Dahl salt-sensitive rats, in vivo sodium transport assay, gastrin-SiO2 microsphere administration, PKC pathway analysis, NHERF1/NHERF2 interaction studies Hypertension High 35674015
2025 Intestinal gastrin/CCKBR reduces glucose absorption by down-regulating intestinal SGLT1 and GLUT2 expressions and stimulating incretin secretion via the PI3K/Akt/eIF4B signaling pathway. Intestinal epithelial cell-specific Cckbr knockout mice on high-fat diet rapidly progressed from pre-diabetes to T2D. Gastrin-SiO2 microspheres reduced intestinal glucose absorption in duodenum from T2D patients. Intestinal epithelial Cckbr knockout mice, HFD model, oral glucose tolerance test, PI3K/Akt/eIF4B signaling analysis, human duodenal tissue studies, Gastrin-SiO2 microsphere administration Advanced science Medium 39950948
2024 Renal gastrin/CCKBR inhibits SGLT2-mediated glucose reabsorption through the Erk/NF-κB signaling pathway. Renal tubule-specific Cckbr knockout mice showed greater susceptibility to obesity and diabetes on high-fat diet. In HK-2 cells, gastrin intervention attenuated high-glucose-induced upregulation of SGLT2, and this effect was absent in the absence of CCKBR. Renal tubule-specific Cckbr knockout mice, HFD + streptozotocin model, HK-2 cell culture with high glucose, Erk/NF-κB pathway western blot, glucose uptake assay Diabetes & metabolism journal Medium 39721589
2012 CCK2R somatic mutations identified in colorectal and gastric cancers increase receptor activity, activate multiple downstream signaling pathways, increase cell migration, and promote angiogenesis. Six mutations in CCK2R were functionally characterized among 140 colorectal and 44 gastric cancers. Functional receptor activity assays, cell migration assay, angiogenesis assay, downstream signaling pathway analysis in cancer cell lines expressing mutant CCK2R Molecular cancer research : MCR Medium 22516348
2012 CCK2R activation by gastrin in GIST xenografts leads to hyper-activation of KIT and PKC-θ kinases and PI3K-AKT pathway over-activation (by western blot), with increased tumor cell proliferation (Ki-67 and mitotic activity). In vivo, gastrin stimulation produced a two-fold increase in GIST tumor volume. GIST xenograft nude mouse model, gastrin administration, western blot (KIT, PKC-θ, PI3K-AKT), IHC (Ki-67, mitotic index) The Journal of pathology Medium 22786615
2007 CCK2R promoter activity requires consensus binding sites for SP1, C/EBP, and GATA transcription factors for transcription in gastric cell lines. Gastrin increases CCK2R transcription through mechanisms partly dependent on PKC and MEK signaling. CCK2R expression is also induced in myofibroblasts (vimentin+, smooth muscle α-actin+, desmin-) adjacent to gastric ulcer repair margins in vivo. Luciferase promoter-reporter constructs with site-directed mutagenesis, qPCR for endogenous CCK2R mRNA, PKC/MEK pharmacological inhibition, gastric cryoulcer injury model, immunofluorescence co-localization Experimental physiology Medium 17933865
2016 miR-148a directly targets the CCKBR 3'UTR (validated by luciferase assay and western blot). CCKBR knockdown by siRNA phenocopied miR-148a overexpression (decreased proliferation and migration). miR-148a anti-oncogenic effects in gastric cancer are mediated through CCKBR-dependent inhibition of STAT3 and Akt activation. Luciferase reporter assay (3'UTR), western blot, siRNA knockdown, proliferation and migration assays, tumor xenograft PloS one Medium 27518872
2013 miR-148a directly targets CCKBR (validated by luciferase reporter assay and western blot) in pancreatic cancer. CCKBR is identified as a functional target mediating miR-148a's effects on proliferation and apoptosis in PANC-1 and AsPC-1 cells. Luciferase reporter assay (3'UTR), western blot, MTT assay, colony formation assay, Annexin V apoptosis assay, caspase activity assay Tumour biology Medium 23975374
2020 mTORC1 inhibition by RAD001 (everolimus) increases CCKBR protein levels (~2.2-fold) and enhances internalization of radiolabeled minigastrin analogue in CCKBR-expressing cells. PP-F11N induces recruitment of β-arrestin1/2 and ERK1/2 phosphorylation upon CCKBR activation. In vivo, RAD001 pretreatment significantly enhanced tumor-specific uptake of [177Lu]Lu-PP-F11N in A431/CCKBR xenograft mice. Kinase inhibitor library screen, western blot (CCKBR protein level, S6 phosphorylation), β-arrestin recruitment assay, ERK1/2 phosphorylation assay, cell internalization assay, xenograft biodistribution, SPECT/CT imaging Theranostics Medium 33042258
2015 CCKAR and CCKBR have dynamic, largely reciprocal expression in embryonic and postnatal brain. Compound homozygous mutant mice lacking both CCK receptors show additive, synergistic defects in cortical development including abnormalities in midline formation, corpus callosum development, and cortical interneuron migration. Compound homozygous double-knockout mice, comparative transcriptome analysis of embryonic neocortex, histological analysis of brain development PloS one Medium 25875176
2026 In the VTA→BLA→BNST circuit, CCK2R in BLA glutamatergic neurons is required for METH-induced conditioned place preference. METH enhanced CCK release from VTA→BLA projections. CCK2R knockout in BLA glutamatergic neurons abolished CPP and normalized synaptic plasticity. CCK2R deletion in this circuit reversed METH-induced increases in AMPA/NMDA ratios, paired-pulse facilitation, and dendritic spine density in BNST. CCKflox/flox cell-type-specific knockout, optogenetics, chemogenetics (DREADD), electrophysiology (AMPA/NMDA ratio, PPF), Golgi staining (dendritic spine density) Translational psychiatry Medium 41888094
2018 Low gastrin/CCKBR is associated with inactivation of ERK/P65 signaling in ER+ breast cancer cells. Gastrin or ERK/P65 activators inhibited ER+ BC through CCKBR-mediated activation of ERK/P65. CCKBR/ERK/P65 signaling functions as tumor suppressive in ER+ BC. CCK-8 proliferation assay, nude mouse xenograft, western blot (ERK, P65 activation), ELISA (serum gastrin) BMC cancer Low 30115027
2015 Trastuzumab upregulates CCKBR protein levels in HER2-negative gastric cancer cells and synergizes with gastrin to enhance CCKBR stability. Combined trastuzumab and gastrin treatment synergistically arrested GC cells at G0/G1 phase and down-regulated AE1, cyclin D1, β-catenin, and cytoplasmic p16, while promoting nuclear translocation of p16 and upregulating AE2. Western blot (CCKBR, AE1, AE2, cyclin D1, β-catenin, p16), flow cytometry (cell cycle), xenograft in vivo model Digestive diseases and sciences Low 26173505
2005 The CCK2R fragment CCK(B)-R(352-379) binds CCK8 peptide with a dissociation constant in the micromolar range, as measured by fluorescence titration in a membrane-mimetic solvent system. This confirms the binding mode of CCK8 with its receptor at this extracellular region. Fluorescence titration spectroscopy in membrane-mimetic solvent Biopolymers Low 15666329
2025 An ensemble of RSG glutamatergic neurons expressing CCKBR (RSGGlu-Cckbr) in layer 5 of the granular retrosplenial cortex encodes opioid-associated memories and controls relapse to opioid via innervation of ZI GABAergic neurons. Cckergic neurons from the anterodorsal thalamus orchestrate RSGGlu-Cckbr–ZI circuit function via CCK release in RSG. Circuit-specific manipulation (optogenetics, chemogenetics), in vivo electrophysiology, opioid CPP behavioral model, calcium imaging bioRxivpreprint Low

Source papers

Stage 0 corpus · 57 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2014 CCK2R identifies and regulates gastric antral stem cell states and carcinogenesis. Gut 96 24951258
2005 A novel mechanism for JAK2 activation by a G protein-coupled receptor, the CCK2R: implication of this signaling pathway in pancreatic tumor models. The Journal of biological chemistry 63 15640156
2016 MiR-148a Functions as a Tumor Suppressor by Targeting CCK-BR via Inactivating STAT3 and Akt in Human Gastric Cancer. PloS one 56 27518872
2013 MiR-148a regulates the growth and apoptosis in pancreatic cancer by targeting CCKBR and Bcl-2. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 49 23975374
1994 Localization of the human cholecystokinin-B/gastrin receptor gene (CCKBR) to chromosome 11p15.5-->p15.4 by fluorescence in situ hybridization. Cytogenetics and cell genetics 43 8222757
2015 Functional synergy between cholecystokinin receptors CCKAR and CCKBR in mammalian brain development. PloS one 40 25875176
2013 Progastrin stimulates colonic cell proliferation via CCK2R- and β-arrestin-dependent suppression of BMP2. Gastroenterology 38 23891976
1995 Chromosomal localization of the gastric and brain receptors for cholecystokinin (CCKAR and CCKBR) in human and mouse. Genomics 37 7759110
2016 Assessment of cholecystokinin 2 receptor (CCK2R) in neoplastic tissue. Oncotarget 36 26910279
2020 Hypergastrinemia Expands Gastric ECL Cells Through CCK2R+ Progenitor Cells via ERK Activation. Cellular and molecular gastroenterology and hepatology 32 32330731
2007 Regulation of mammalian gastrin/CCK receptor (CCK2R) expression in vitro and in vivo. Experimental physiology 27 17933865
2018 Exploiting the Concept of Multivalency with 68Ga- and 89Zr-Labelled Fusarinine C-Minigastrin Bioconjugates for Targeting CCK2R Expression. Contrast media & molecular imaging 23 29849512
2015 Selective Tumor Targeting of Desacetyl Vinblastine Hydrazide and Tubulysin B via Conjugation to a Cholecystokinin 2 Receptor (CCK2R) Ligand. Molecular pharmaceutics 23 26043355
2014 Therapeutic application of CCK2R-targeting PP-F11: influence of particle range, activity and peptide amount. EJNMMI research 21 26116111
2022 Intestinal Gastrin/CCKBR (Cholecystokinin B Receptor) Ameliorates Salt-Sensitive Hypertension by Inhibiting Intestinal Na+/H+ Exchanger 3 Activity Through a PKC (Protein Kinase C)-Mediated NHERF1 and NHERF2 Pathway. Hypertension (Dallas, Tex. : 1979) 18 35674015
2020 Pharmacological inhibition of mTORC1 increases CCKBR-specific tumor uptake of radiolabeled minigastrin analogue [177Lu]Lu-PP-F11N. Theranostics 18 33042258
2007 Pre-clinical evaluation of a new orally-active CCK-2R antagonist, Z-360, in gastrointestinal cancer models. Regulatory peptides 18 17961733
2013 Multifactorial diagnostic NIR imaging of CCK2R expressing tumors. Biomaterials 17 23591397
2012 Promoting role of cholecystokinin 2 receptor (CCK2R) in gastrointestinal stromal tumour pathogenesis. The Journal of pathology 17 22786615
2001 Polymorphisms of the CCK, CCKAR and CCKBR genes: an association with alcoholism study. Journal of studies on alcohol 16 11513220
2020 Initial In Vitro and In Vivo Evaluation of a Novel CCK2R Targeting Peptide Analog Labeled with Lutetium-177. Molecules (Basel, Switzerland) 15 33049999
2012 Somatic mutations in CCK2R alter receptor activity that promote oncogenic phenotypes. Molecular cancer research : MCR 15 22516348
2022 Cholecystokinin (CCK) and its receptors (CCK1R and CCK2R) in chickens: functional analysis and tissue expression. Poultry science 14 36436379
2018 Low serum gastrin associated with ER+ breast cancer development via inactivation of CCKBR/ERK/P65 signaling. BMC cancer 13 30115027
2020 CCK2R antagonists: from SAR to clinical trials. Drug discovery today 12 32439608
2015 Trastuzumab Inhibits Growth of HER2-Negative Gastric Cancer Cells Through Gastrin-Initialized CCKBR Signaling. Digestive diseases and sciences 12 26173505
2022 Introduction of a SiFA Moiety into the D-Glutamate Chain of DOTA-PP-F11N Results in Radiohybrid-Based CCK-2R-Targeted Compounds with Improved Pharmacokinetics In Vivo. Pharmaceuticals (Basel, Switzerland) 11 36558917
2023 Rapid Generation and Molecular Docking Analysis of Single-Chain Fragment Variable (scFv) Antibody Selected by Ribosome Display Targeting Cholecystokinin B Receptor (CCK-BR) for Reduction of Chronic Neuropathic Pain. International journal of molecular sciences 10 37446213
2018 Multimerization results in formation of re-bindable metabolites: A proof of concept study with FSC-based minigastrin imaging probes targeting CCK2R expression. PloS one 10 30059514
2013 Identification of novel amino acid derived CCK-2R antagonists as potential antiulcer agent: homology modeling, design, synthesis, and pharmacology. Journal of chemical information and modeling 10 23240656
2025 Elucidating pathway-selective biased CCKBR agonism for Alzheimer's disease treatment. Cell 9 41270732
2019 UCN3 suppresses food intake in coordination with CCK and the CCK2R in Siberian sturgeon (Acipenser baerii). Comparative biochemistry and physiology. Part A, Molecular & integrative physiology 8 31051262
2017 177Lu Labeled Cyclic Minigastrin Analogues with Therapeutic Activity in CCK2R Expressing Tumors: Preclinical Evaluation of a Kit Formulation. Molecular pharmaceutics 8 28728415
2024 CCKBR+ cancer cells contribute to the intratumor heterogeneity of gastric cancer and confer sensitivity to FOXO inhibition. Cell death and differentiation 7 39164456
2021 Pseudomonas Exotoxin A-Based Immunotherapy Targeting CCK2R-Expressing Colorectal Malignancies: An In Vitro and In Vivo Evaluation. Molecular pharmaceutics 7 33998814
2021 Therapeutic Response of CCKBR-Positive Tumors to Combinatory Treatment with Everolimus and the Radiolabeled Minigastrin Analogue [177Lu]Lu-PP-F11N. Pharmaceutics 7 34959437
2013 rG17PE38, a novel immunotoxin target to gastric cancer with overexpressed CCK-2R. Journal of drug targeting 7 23311704
2023 Effect of N-Terminal Peptide Modifications on In Vitro and In Vivo Properties of 177Lu-Labeled Peptide Analogs Targeting CCK2R. Pharmaceutics 6 36986657
2025 Intestinal Gastrin/CCKBR Axis Protects against Type 2 Diabetes by Reducing Intestinal Glucose Absorption through the PI3K/Akt/eIF4B Signaling Pathway. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 5 39950948
2024 Kidney Gastrin/CCKBR Attenuates Type 2 Diabetes Mellitus by Inhibiting SGLT2-Mediated Glucose Reabsorption through Erk/NF-κB Signaling Pathway. Diabetes & metabolism journal 5 39721589
2024 Acidity-Triggered "Sticky Spotlight": CCK2R-Targeted TME-Sensitive NIR Fluorescent Probes for Tumor Imaging In Vivo. Bioconjugate chemistry 4 38514970
2024 Biodistribution Assessment of a Novel 68Ga-Labeled Radiopharmaceutical in a Cancer Overexpressing CCK2R Mouse Model: Conventional and Radiomics Methods for Analysis. Life (Basel, Switzerland) 4 38541733
2023 Intestinal Cckbr-specific knockout mouse as a novel model of salt-sensitive hypertension via sodium over-absorption. Journal of geriatric cardiology : JGC 4 37576480
2022 Downregulation of CCKBR Expression Inhibits the Proliferation of Gastric Cancer Cells, Revealing a Potential Target for Immunotoxin Therapy. Current cancer drug targets 4 34994328
2005 Receptor fragment approach to the binding between CCK8 peptide and cholecystokinin receptors: a fluorescence study on type B receptor fragment CCK(B)-R (352-379). Biopolymers 4 15666329
2022 The expression of the gastrin/cholecystokinin (GAST/CCK) family and their receptors (CCKAR/CCKBR) in the chicken changes in response to quantitative restriction and reveals a functional role of CCK in the crop. General and comparative endocrinology 3 35292263
2014 The investigation of membrane binding by amphibian peptide agonists of CCK2R using (31)P and (2)H solid-state NMR. Peptides 3 24582625
2025 Advances in radiopharmaceuticals for cancer radiotheranostics: CCK2R targeting as a paradigm for translational innovation. Cancer communications (London, England) 2 40974551
2024 Development and Validation of Novel Z-360-Based Macromolecules for the Active Targeting of CCK2-R. Molecular pharmaceutics 2 38959127
2023 Deterioration of apatite orientation in the cholecystokinin B receptor gene (Cckbr)-deficient mouse femurs. Journal of bone and mineral metabolism 2 37676507
2026 Gastrin-dependent expansion of Cck2r+ corpus progenitors accelerates ulcer healing and inhibits gastric dysplasia. Gut 1 40983503
2026 Paving the Way for CCK2R-Targeted Peptide Receptor Radionuclide Therapy with [177Lu]Lu-DOTA-MGS5 in Patients with Small Cell Lung Cancer. Pharmaceutics 0 41599245
2026 CCK2R regulates METH-induced CPP acquisition within VTA-BLA-BNST circuit in male mice. Translational psychiatry 0 41888094
2025 Dimeric CCK2R radiotheranostic tracers synergize with mTOR inhibition for enhanced tumor therapy. Theranostics 0 40963930
2025 Discovery of a β-arrestin-biased CCKBR agonist that blocks CCKBR-dependent long-term potentiation. Nature communications 0 41360797
2025 Cholecystokinin (CCK) mediates CCKBR to regulate androgen secretion via the steroid pathway in Bactrian camel Sertoli cells. The Journal of steroid biochemistry and molecular biology 0 41411793
2024 Low expression of CCKBR in the acinar cells is associated with insufficient starch hydrolysis in ruminants. Communications biology 0 39706905

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