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Receptor for gastrin and cholecystokinin. The CCK-B receptors occur throughout the central nervous system where they modulate anxiety, analgesia, arousal, and neuroleptic activity. This receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system.; Isoform 2 is constitutively activated and may regulate cancer cell proliferation via a gastrin-independent mechanism.
Gene References into Functions
We concluded that low serum gastrin is related to increased risk of ER(+) BC development. The results also established that CCKBR/ERK/P65 signaling function is generally tumor suppressive in ER(+) BC, indicating therapies should focus on restoring, not inhibiting, CCKBR/ERK/P65 pathway activity. PMID: 30115027
High CCK2R expression is associated with cancer. PMID: 26910279
These results suggest that Z-360 exerts an anti-tumor effect through a reduction in anti-apoptosis factors by blocking CCK2R PMID: 28739697
High CCK-BR expression is associated with Gastric Cancer. PMID: 27518872
There is no identifiable link between nuclear CCK2R expression and all the clinicopathological characteristics examined in a cohort of Taiwanese colon cancer patients. PMID: 26508021
Data indicate that variant c.811+32C>A in cholecystokinin-B receptor gene (CCKBR) does not have a significant impact on pancreatic cancer risk or survival in a Hungarian cohort. PMID: 26646278
This study showed that CCK2 receptors were highly expressed within the cytoplasmic area of cancerous cells, whereas the levels were very low in normal tissues. PMID: 26520651
CCK-BR SNP predicts survival and should be studied as a candidate genetic biomarker for those at risk of pancreatic cancer. PMID: 25469546
treatment with gastrin, a CCK2R agonist, stimulated the secretion of GLP-1, and that this effect was likely due to increased expression of proglucagon and PCSK1 (also known as prohormone convertase 3 (PC3 gene)). PMID: 25601282
Our results indicate a promoting role of CCK2R on GIST tumourigenesis, particularly in tumours of gastric origin. PMID: 22786615
The gastrin receptor is a promising tumor cell surface target for future prostate-cancer-specific imaging applications. PMID: 24211650
DeltaFosB induction in prelimbic area occurred selectively in susceptible mice after chronic social defeat stress and produced these effects partly through induction of the cholecystokinin (CCK)-B receptor. PMID: 24623766
some CCKBR polymorphisms may contribute to an underlying predisposition towards suicidal behaviour in bipolar disorder. PMID: 23890582
Gastric mucosal injury with H. pylori infection destroys the pH barrier on the foveolar epithelium and may induce gastrin receptor expression through pH changes. PMID: 23053898
Suggest that CCK2R-mediated COX-2 up-regulation via JAK2/STAT3/PI3K/Akt pathway is involved in the proliferative effect of gastrin on human gastric cancer cells. PMID: 23376640
Data suggest that mutations in cholecystokinin 2 receptor (CCK2R) may promote tumorigenesis through deregulated receptor activity and highlight the importance of evaluating CCK2R inhibitors to block both the normal and mutant forms of the receptor. PMID: 22516348
These results show the importance of the CCK-BR in regulation of growth and apoptosis in pancreatic cancer. PMID: 22442157
A novel splice variant acting as a dominant negative on membrane density of the CCK2R may be of importance for the pathophysiology of certain tumors and for their in vivo CCK2R-targeting. PMID: 22040601
A single nucleotide polymorphism in the cholecystokinin-B receptor that alters splicing predicts survival in pancreatic cancer. PMID: 22277584
proximal DNA elements within the human gastrin gene promoter mediate interactions between JunD, which induces gastrin gene expression and menin, which suppresses JunD-mediated activation. PMID: 21852362
Genetic polymorphisms in cholecystokinin B receptor may play a role in antipsychotic induced weight gain in schizophrenia patients. PMID: 20732371
Regulation of membrane cholecystokinin-2 receptor by agonists enables classification of partial agonists as biased agonists. PMID: 21156802
a positive-feedback loop whereby gastrin, acting via the CCK2 receptor, increases its own expression PMID: 20932834
The CCK(2)splice variant with retention of intron 4 (Ri4sv) is a marker of specific gastrointestinal and lung tumours. PMID: 19627395
The cholecystokinin 2 receptor allele with 21 CT repeats was associated with multiple chemical sensitivity when compared in post hoc analyses with all individuals from the population sample. PMID: 20185366
Results show that signaling through ACAT/cholesterol esterification is a novel pathway for the CCK2R that contributes to tumor cell proliferation and invasion. PMID: 19502590
Expression of gastrin and cholecystokinin 2 (CCK(2)) receptor splice variants are upregulated in human colonic adenomas where they are thought to contribute to tumor growth and progression. PMID: 19697327
A misspliced form of the cholecystokinin-B/gastrin receptor in pancreatic carcinoma: role of reduced sellular U2AF35 and a suboptimal 3'-splicing site leading to retention of the fourth intron. PMID: 11830556
hGARE is proposed as a new candidate target gene in microsatellite instability tumorigenesis. PMID: 11896205
Hyper-gastrinaemia may promote proliferation of human colonic adenomas that expressnon-truncated CCK-2 receptor isoforms. PMID: 12189558
data represent the first evidence for role in regulating cell-cell and cell-substrate adhesion and support a role in the progression of carcinoma PMID: 12400008
data support the hypothesis that cholecystokinin-B receptor mediated activation of the hypothalamic-pituitary-adrenal axis is relatively resistant to cortisol feedback inhibition PMID: 12510010
induction by oncogenic ras in LoVo and Colo320HSR colon cancer cell lines PMID: 12761477
Cholecystokinin-A receptor and B receptor polymorphisms, considered alone, showed no correlation with hallucinations in Parkinson's disease PMID: 12777967
this is the first report that provides evidence for the high tumorigenic effect of a constitutively active CCK2R mutant, thus raising a potential role of the CCK2R in human cancer. PMID: 12955087
findings suggest physiological functions for the CCK(2)R in calcitonin-secretion and gene expression as well as a pathophysiological role in medullary thyroid carcinoma proliferation PMID: 14759564
CCK exerts secretagogue action on human ZG cells, acting through CCK2-Rs coupled to the adenylate cyclase/protein kinase A signaling cascade PMID: 15001623
A role is implicated for the CCKB receptor gene in suicide completers, the highest gene expression being observed in the cerebellum followed by cingulate gyrus and pre-frontal cortex compared to their age and sex-matched controls. PMID: 15036586
Gastrin/CCK-B receptor autocrine or paracrine pathway may possibly play an important role in the progression of gastric cancer. PMID: 15040018
CCK2i4svR, a splice variant of cholecystokinin-2 receptor, has a role in agonist-independent activation of Src tyrosine kinase PMID: 15292208
Findings are consistent with the notion that genetic variation in the CCK B receptor neurotransmitter system contributes to the pathogenesis of panic disorder. PMID: 15354400
the MEK1/ERK1/2 pathway couples the CCK2 receptor to nuclearization and DNA binding of Egr-1 PMID: 15611055
analysis of interspecies polymorphism in the human and rat cholecystokinin receptor-2 and its effect on the cholecystokinin binding site PMID: 15817487
Photoaffinity labeling of the type B CCK receptor provides evidence for the peptide-binding domain to include receptor loop and amino-terminal tail regions residing at the extracellular surface of the plasma membrane. PMID: 15850403
human normal, inflammatory, and malignant gastric tissues simultaneously express the classical and alternative splicing cholecystokinin-B/gastrin receptor genes PMID: 15989082
Study confirms that a high proportion of gastric cancer tissue samples express the gastrin/CCKB receptor, which can stimulate the growth of gastrin/CCKB receptor-positive gastric cancer cells. PMID: 16012719
CCK2 gastrin receptor may have a role in leukemia PMID: 16142371
Gastrin exerts an antiproliferative and proapoptotic effect on human colon cancer cells expressing the wild-type CCK2 receptor. PMID: 16143134
The expression rates of gastrin and gastrin receptor are high (about a half) in gastric carcinoma tissues, and there is an association between gastrin and gastrin receptor expression. PMID: 16228228
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Subcellular Location
Cell membrane; Multi-pass membrane protein.
Protein Families
G-protein coupled receptor 1 family
Tissue Specificity
Isoform 1 is expressed in brain, pancreas, stomach, the colon cancer cell line LoVo and the T-lymphoblastoma Jurkat, but not in heart, placenta, liver, lung, skeletal muscle, kidney or the stomach cancer cell line AGS. Expressed at high levels in the smal