GO:0031741 type B gastrin/cholecystokinin receptor binding: Mechanism, Genes and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0031741 defines the molecular function of binding to a type B gastrin/cholecystokinin receptor (CCK-B/gastrin receptor), a class A GPCR.
• The term is a ligand-side molecular function; the receptor itself is encoded by CCKBR (also known as CCK2R) and is expressed in the stomach, pancreas, kidney, brain, and immune cells.
• Ligand binding to CCK-B receptors activates phospholipase C and protein kinase C signaling in pancreatic and cancer cells.
• Gastrin/CCK-B receptor binding regulates gene expression, including VMAT2 and PAI-2, linking the term to neuroendocrine and cancer biology.
• The CCK-B receptor antagonist PD-136,450 acts as a partial agonist in the stomach and a full agonist in the pancreas, showing tissue-specific pharmacology.
• CRISPR knockout, point-mutation, knock-in, and overexpression models are essential to dissect ligand-receptor binding and downstream signaling.
Description
GO:0031741, type B gastrin/cholecystokinin receptor binding, is a molecular function term that describes the binding of a ligand to the type B gastrin/cholecystokinin receptor (CCK-B receptor, also called CCK2 receptor). This receptor is a G protein-coupled receptor that mediates the actions of the peptide hormones gastrin and cholecystokinin in the gastrointestinal tract, pancreas, kidney, and central nervous system. The term captures the ligand-side event that initiates receptor activation and downstream signaling, making it central to understanding how gastrin and cholecystokinin exert their physiological and pathological effects. Researchers study this term to clarify how extracellular ligands engage the receptor and how this interaction is coupled to intracellular responses such as phospholipase C activation and protein kinase C signaling. Because dysregulated gastrin/CCK-B receptor signaling is implicated in gastrointestinal and pancreatic cancers, as well as in immune cell function, the term is relevant to both basic biology and translational research.
type B gastrin/cholecystokinin receptor binding At A Glance
| GO ID | GO:0031741 |
|---|---|
| GO term | type B gastrin/cholecystokinin receptor binding |
| Ontology | molecular_function |
| Synonym | type B gastrin/cholecystokinin receptor ligand |
| Major function | Binding of ligands such as gastrin and cholecystokinin to the type B gastrin/cholecystokinin receptor (CCK-B/CCK2 receptor) |
| Receptor family | Class A G protein-coupled receptor (GPCR) |
| Primary ligands | Gastrin, cholecystokinin (CCK) |
| Tissue expression | Stomach, pancreas, kidney, brain, immune cells |
| Downstream signaling | Phospholipase C activation, protein kinase C signaling |
What Is GO:0031741?
According to the Gene Ontology, GO:0031741 is defined as binding to a type B gastrin/cholecystokinin receptor. In other words, it is the molecular function of a ligand (such as gastrin or cholecystokinin) that physically interacts with the CCK-B/gastrin receptor. This function is distinct from the receptor's own signaling activity; it specifically describes the binding event from the ligand perspective. The synonym type B gastrin/cholecystokinin receptor ligand reflects this ligand-centric view. The term is used in annotations where a gene product binds to the CCK-B receptor, and it is supported by experimental evidence such as radioligand binding, receptor autoradiography, and functional assays in tissues including kidney, stomach, pancreas, and immune cells.
Why Is type B gastrin/cholecystokinin receptor binding Important in Cell Biology?
GO:0031741 is important because it defines the initial molecular event that triggers CCK-B receptor signaling, which controls acid secretion, pancreatic enzyme release, cell proliferation, and gene expression. Dysregulation of this binding function is linked to gastrointestinal and pancreatic cancers, where receptor activation promotes mitogenic signaling. The term also matters for immunology, as functional CCK-B receptors are present on human T lymphoblastoid cells, suggesting a role in immune modulation. In the kidney, CCK-B receptors have been molecularly and pharmacologically characterized, indicating broader physiological roles beyond the gut. Understanding this binding function at the atomic and cellular level can guide the development of receptor antagonists and agonists with tissue-specific effects.
• Defines the ligand-receptor interaction that initiates gastrin and cholecystokinin signaling.
• Controls gastric acid secretion and pancreatic enzyme release through CCK-B receptor activation.
• Regulates gene expression, including VMAT2 and PAI-2, via gastrin/CCK-B receptor binding.
• Implicated in gastrointestinal and pancreatic cancer cell proliferation and survival.
• Expressed in immune cells, suggesting a role in neuroimmune communication.
• Provides a target for pharmacological antagonists such as PD-136,450 with tissue-specific agonist activity.
• Enables mechanistic studies of GPCR coupling to phospholipase C and protein kinase C.
• Supports cross-species and cross-tissue comparisons of receptor pharmacology.
• Facilitates development of CRISPR models to test ligand-binding residues and signaling motifs.
• Links peptide hormone biology to kidney, brain, and immune system functions.
Molecular Mechanism of type B gastrin/cholecystokinin receptor binding
Ligand recognition and binding pocket
In simple terms: The ligand docks into a specific pocket on the receptor, like a key in a lock.
The type B gastrin/cholecystokinin receptor (CCK-B/CCK2 receptor) is a class A GPCR that binds gastrin and cholecystokinin with high affinity. Binding occurs at the extracellular surface of the receptor, where ligand-specific residues determine selectivity. Studies using radioligand binding and receptor autoradiography in kidney and stomach tissues have demonstrated saturable, specific binding sites for gastrin/CCK-B ligands. The receptor's third intracellular loop, particularly the valine-286 residue, plays a pivotal role in coupling ligand binding to intracellular signal transduction in human colon cancer cells.
Receptor activation and G protein coupling
In simple terms: Once the ligand binds, the receptor changes shape and activates G proteins inside the cell.
Ligand binding to the CCK-B receptor induces conformational changes that promote G protein activation. In pancreatic AR4-2J tumoral cells, gastrin/CCK-B receptor coupling leads to phospholipase C activation and protein kinase C signaling. This pathway generates inositol trisphosphate and diacylglycerol, mobilizing calcium and activating downstream kinases. The valine-286 residue in the third intracellular loop is critical for this coupling, as mutations at this site alter signal transduction in colon cancer cells.
Tissue-specific pharmacology and agonist behavior
In simple terms: The same drug can act differently in different organs, like a partial switch in the stomach and a full switch in the pancreas.
The CCK-B receptor antagonist PD-136,450 behaves as a partial secretory agonist in the rat stomach but as a full agonist in the rat pancreas. This tissue-specific pharmacology indicates that ligand binding at GO:0031741 can produce context-dependent outcomes, likely due to differences in receptor coupling efficiency or accessory proteins. Such findings are important for drug development, as they show that targeting the binding event may have organ-specific effects.
Downstream gene regulation
In simple terms: Binding at the receptor can switch genes on or off, changing cell behavior.
Gastrin binding to CCK-B receptors induces expression and promoter activity of the vesicular monoamine transporter subtype 2 (VMAT2). Additionally, gastrin regulates plasminogen activator inhibitor-2 (PAI-2) through Rho GTPase and menin-dependent pathways. These examples show that the binding function described by GO:0031741 is coupled to transcriptional programs relevant to neuroendocrine and cancer biology.
Receptor expression in immune and kidney tissues
In simple terms: The receptor is not only in the gut; it also appears in immune cells and kidneys.
Functional gastrin-CCK-B type receptors are present on human T lymphoblastoid Jurkat cells, suggesting a role in immune cell signaling. In the kidney, CCK-B receptors have been molecularly, pharmacologically, and functionally characterized, with specific localization patterns. These findings broaden the physiological scope of GO:0031741 beyond the gastrointestinal tract and highlight the importance of tissue context in studying ligand binding.
Key Genes Involved in GO:0031741 type B gastrin/cholecystokinin receptor binding
The following genes and proteins are central to type B gastrin/cholecystokinin receptor binding and its downstream biology.
| Gene | Major Role | Research Relevance |
|---|---|---|
| CCKBR (CCK2R) | Encodes the type B gastrin/cholecystokinin receptor | Primary receptor for GO:0031741; target for binding assays and mutagenesis |
| GAST | Encodes gastrin, a major ligand for CCKBR | Ligand-side regulator of binding; studied in acid secretion and cancer |
| CCK | Encodes cholecystokinin, a ligand for CCKBR | Alternative ligand; relevant to pancreatic and neural functions |
| VMAT2 (SLC18A2) | Gastrin-regulated gene; vesicular monoamine transporter | Downstream target of CCKBR binding; marker of neuroendocrine regulation |
| PAI-2 (SERPINB2) | Gastrin-regulated gene; protease inhibitor | Downstream effector linked to Rho GTPase and menin |
| MEN1 | Menin, tumor suppressor involved in PAI-2 regulation | Connects CCKBR signaling to endocrine tumor biology |
| RHOA | Rho GTPase, mediates gastrin-induced PAI-2 expression | Signaling intermediate downstream of CCKBR binding |
| PLCB | Phospholipase C beta, downstream of CCKBR | Mediates IP3/DAG signaling after ligand binding |
| PRKC | Protein kinase C, downstream of CCKBR | Effector of CCKBR-mediated signaling |
| GNAQ/GNA11 | G alpha q/11 proteins coupling to CCKBR | G protein partners for CCKBR activation |
| EGFR | Epidermal growth factor receptor, transactivation target | Cross-talk with CCKBR signaling in cancer |
| MAPK1/3 | ERK1/2 kinases, downstream of CCKBR | Proliferative signaling after ligand binding |
| JUN/FOS | AP-1 transcription factors | Immediate early genes activated by CCKBR signaling |
| NFKB1 | NF-kB subunit, potential downstream target | Inflammatory signaling linked to CCKBR in immune cells |
| SRC | Proto-oncogene tyrosine kinase | Potential mediator of CCKBR-dependent proliferation |
| STAT3 | Signal transducer and activator of transcription 3 | Candidate downstream effector in CCKBR-driven cancer |
| CDKN1A | p21, cell cycle inhibitor | May be modulated by CCKBR signaling in cancer cells |
| BCL2 | Anti-apoptotic protein | Survival signaling downstream of CCKBR |
How Is type B gastrin/cholecystokinin receptor binding Regulated?
The binding function described by GO:0031741 is regulated at multiple levels. Receptor availability is controlled by CCKBR gene expression, which varies by tissue and can be influenced by hormonal and inflammatory signals. Ligand availability depends on gastrin and CCK synthesis, processing, and secretion. At the receptor level, the third intracellular loop, particularly valine-286, regulates coupling efficiency to downstream effectors such as phospholipase C and protein kinase C. Additionally, tissue-specific factors modulate the pharmacological behavior of ligands, as shown by the partial agonist activity of PD-136,450 in the stomach versus full agonist activity in the pancreas. Downstream feedback through Rho GTPase and menin pathways further shapes the transcriptional output of CCKBR binding.
type B gastrin/cholecystokinin receptor binding and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| CCKBR | Colon cancer, pancreatic cancer, gastric acid disorders | CCKBR knockout and point-mutation cell lines (e.g., colon cancer cells) |
| GAST | Gastrinoma, gastric acid hypersecretion | GAST overexpression in neuroendocrine cells |
| PAI-2 (SERPINB2) | Cancer progression, fibrosis | PAI-2 knockout and knock-in models |
| MEN1 | Multiple endocrine neoplasia type 1 | MEN1 knockout cell models |
| VMAT2 (SLC18A2) | Neuroendocrine tumors, Parkinson's disease | VMAT2 reporter and overexpression models |
Gastrointestinal and pancreatic cancer
CCK-B receptor binding and downstream signaling are implicated in gastrointestinal and pancreatic cancer. In human colon cancer cells, the valine-286 residue in the third intracellular loop of the CCK2 receptor is pivotal for intracellular signal transduction, linking ligand binding to proliferative and survival pathways. Gastrin-regulated genes such as PAI-2 are controlled through Rho GTPase and menin, connecting CCKBR binding to tumor suppressor pathways. These findings suggest that dysregulated GO:0031741 activity can contribute to cancer progression.
Neuroendocrine and gastric acid secretion disorders
Gastrin/CCK-B receptor binding regulates gastric acid secretion and pancreatic enzyme release. The CCK-B receptor antagonist PD-136,450 acts as a partial secretory agonist in the stomach and a full agonist in the pancreas, indicating that pharmacological modulation of binding can have tissue-specific effects relevant to acid-peptic disorders. Gastrin-induced VMAT2 expression further links CCKBR binding to neuroendocrine regulation.
Immune and renal biology
Functional gastrin-CCK-B receptors are present on human T lymphoblastoid Jurkat cells, suggesting a role for GO:0031741 in immune cell signaling. In the kidney, CCK-B receptors have been characterized molecularly and pharmacologically, with specific localization, indicating potential roles in renal physiology and disease. These findings expand the disease relevance of CCKBR binding beyond the gastrointestinal tract.
From type B gastrin/cholecystokinin receptor binding-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does CCKBR mediate gastrin-induced proliferation? | CCKBR knockout in colon cancer cell lines |
| Which residues are required for ligand binding? | Point mutations in CCKBR extracellular loops |
| How does valine-286 affect signal transduction? | Valine-286 point-mutant knock-in in cancer cells |
| Can tissue-specific agonist activity be reproduced? | Tissue-specific CCKBR overexpression in stomach vs. pancreas models |
| What genes are regulated by CCKBR binding? | Knock-in of tagged CCKBR followed by RNA-seq |
| Is CCKBR binding required for immune cell activation? | CCKBR knockout in Jurkat T cells |
How to Study the type B gastrin/cholecystokinin receptor binding Process
| Method | What It Measures | Typical Application |
|---|---|---|
| Radioligand binding | Affinity and specificity of ligand-receptor interaction | Characterizing CCKBR pharmacology in tissues |
| Phospholipase C assay | Enzymatic activity downstream of CCKBR | Measuring receptor coupling in pancreatic cells |
| Protein kinase C assay | Kinase activation after ligand binding | Assessing downstream signaling in cancer cells |
| RNA-seq | Transcriptional changes induced by CCKBR binding | Identifying gastrin-regulated genes |
| Promoter-reporter assay | Promoter activity of target genes | Validating VMAT2 regulation by gastrin |
| Receptor autoradiography | Localization of CCKBR binding sites | Mapping receptor distribution in kidney and stomach |
| Immunohistochemistry | Protein expression and localization | Confirming CCKBR expression in tissues |
| CRISPR knockout | Loss-of-function effects on binding and signaling | Testing causality of CCKBR in cancer cells |
Radioligand binding assays
Radioligand binding assays using labeled gastrin or CCK analogs are used to measure affinity, saturability, and specificity of type B gastrin/cholecystokinin receptor binding. These assays can be performed on membrane preparations from tissues such as kidney, stomach, and pancreas, and are essential for pharmacological characterization of the receptor.
Signal transduction assays
Downstream signaling after CCKBR binding can be measured by assessing phospholipase C activity, inositol phosphate production, calcium mobilization, and protein kinase C activation. In pancreatic AR4-2J cells, coupling of gastrin/CCKB receptors to phospholipase C and protein kinase C has been demonstrated. In colon cancer cells, valine-286-dependent signal transduction can be monitored using reporter assays and kinase activity measurements.
Gene expression analysis
RNA-seq and promoter-reporter assays are used to identify genes regulated by CCKBR binding, such as VMAT2 and PAI-2. Gastrin-induced VMAT2 expression and promoter activity can be quantified in appropriate cell models. PAI-2 regulation through Rho GTPase and menin can be dissected using knockdown and overexpression approaches.
Imaging and localization
Receptor autoradiography and immunohistochemistry are used to localize CCK-B receptors in tissues such as kidney and stomach. Fluorescently tagged ligands or receptors can be used for live-cell imaging of binding and internalization. These methods help confirm tissue-specific expression patterns and binding sites.
How CRISPR Can Be Used to Study GO:0031741 type B gastrin/cholecystokinin receptor binding
Knockout
CRISPR knockout of CCKBR is used to eliminate receptor expression and test whether type B gastrin/cholecystokinin receptor binding is required for downstream signaling and cellular phenotypes. For example, knocking out CCKBR in colon cancer cells can reveal whether gastrin-induced proliferation depends on this receptor. Knockout models are also useful for validating ligand specificity in tissues such as the kidney and immune cells.
Point Mutation
Point mutations in CCKBR, such as valine-286 in the third intracellular loop, can be introduced using CRISPR to dissect structure-function relationships. These models help determine which residues are critical for ligand binding versus G protein coupling. Point-mutant knock-in cell lines are valuable for testing whether specific amino acids regulate signal transduction in cancer cells.
Knock-in
Knock-in of tagged or reporter-linked CCKBR allows real-time monitoring of receptor expression, localization, and binding dynamics. Tagged knock-in models can be used with imaging and proteomics to identify interacting partners after ligand binding. Knock-in of disease-associated variants can also help assess their impact on receptor function.
Overexpression
Overexpression of CCKBR or its ligands (gastrin, CCK) is used to amplify signaling and study downstream effects such as VMAT2 and PAI-2 regulation. Overexpression models can reveal tissue-specific responses, as seen with the partial versus full agonist activity of PD-136,450 in stomach and pancreas. These models are also useful for drug screening and dose-response studies.
How EDITGENE Supports type B gastrin/cholecystokinin receptor binding Research
Researchers studying type B gastrin/cholecystokinin receptor binding-related genes often need to determine whether a candidate gene is causally involved in ligand binding, receptor activation, or downstream signaling. EDITGENE provides CRISPR-based cell model services that enable precise genetic manipulation to answer these questions.
Contact EDITGENE today to design your custom CRISPR model for type B gastrin/cholecystokinin receptor binding research.
Frequently Asked Questions About type B gastrin/cholecystokinin receptor binding
What is GO:0031741?
GO:0031741 is the Gene Ontology molecular function term for type B gastrin/cholecystokinin receptor binding, defined as binding to a type B gastrin/cholecystokinin receptor.
What genes are involved in type B gastrin/cholecystokinin receptor binding?
The primary gene is CCKBR, which encodes the receptor. Ligands include gastrin (GAST) and cholecystokinin (CCK). Downstream genes include VMAT2 and PAI-2.
What is the type B gastrin/cholecystokinin receptor?
It is a class A G protein-coupled receptor, also known as CCK-B or CCK2 receptor, that binds gastrin and cholecystokinin and signals through phospholipase C and protein kinase C.
Where is the type B gastrin/cholecystokinin receptor expressed?
It is expressed in the stomach, pancreas, kidney, brain, and immune cells such as T lymphoblastoid Jurkat cells.
How does type B gastrin/cholecystokinin receptor binding affect cancer?
Binding activates proliferative and survival signaling in colon and pancreatic cancer cells, partly through the valine-286 residue and downstream pathways.
What drugs target type B gastrin/cholecystokinin receptor binding?
The antagonist PD-136,450 targets this receptor and shows partial agonist activity in the stomach and full agonist activity in the pancreas.
What methods are used to study type B gastrin/cholecystokinin receptor binding?
Radioligand binding, phospholipase C assays, protein kinase C assays, RNA-seq, and receptor autoradiography are commonly used.
How can CRISPR help study type B gastrin/cholecystokinin receptor binding?
CRISPR knockout, point mutation, knock-in, and overexpression models can test the role of CCKBR and its ligands in binding and signaling.
Is type B gastrin/cholecystokinin receptor binding involved in immune function?
Yes, functional receptors are present on human T lymphoblastoid Jurkat cells, suggesting a role in immune signaling.
What is the synonym for GO:0031741?
The synonym is type B gastrin/cholecystokinin receptor ligand.
Conclusion
GO:0031741, type B gastrin/cholecystokinin receptor binding, is a molecular function that captures the critical ligand-receptor interaction initiating gastrin and cholecystokinin signaling. Its roles span gastric acid secretion, pancreatic function, gene regulation, cancer biology, and immune cell signaling. Understanding this binding event at the molecular level provides a foundation for therapeutic targeting and for dissecting tissue-specific pharmacology. CRISPR-based cell models are powerful tools to test causality and refine our knowledge of this important interaction.
References
- 1. de Weerth A et al.. 1998. Gastrin/cholecystokinin type B receptors in the kidney: molecular, pharmacological, functional characterization, and localization.. Eur J Clin Invest 28(7):592-601 PMID: 9726041
- 2. Schmassmann A et al.. 1994. Cholecystokinin type B receptor antagonist PD-136,450 is a partial secretory agonist in the stomach and a full agonist in the pancreas of the rat.. Gut 35(2):270-4 PMID: 8307482
- 3. Dornand J et al.. 1995. Gastrin-CCK-B type receptors on human T lymphoblastoid Jurkat cells.. Am J Physiol 268(3 Pt 1):G522-9 PMID: 7900813
- 4. Seva C et al.. 1994. Coupling of pancreatic gastrin/cholecystokinin-B (G/CCKB) receptors to phospholipase C and protein kinase C in AR4-2J tumoral cells.. Regul Pept 52(1):31-8 PMID: 7972929
- 5. Yu HG et al.. 2005. Valine-286 residue in the third intracellular loop of the cholecystokinin 2 receptor exerts a pivotal role in cholecystokinin 2 receptor mediated intracellular signal transduction in human colon cancer cells.. Cell Signal 17(12):1505-15 PMID: 15951156
- 6. Gerhard M et al.. 2001. Gastrin induces expression and promoter activity of the vesicular monoamine transporter subtype 2.. Endocrinology 142(8):3663-72 PMID: 11459816
- 7. Varro A et al.. 2002. Identification of plasminogen activator inhibitor-2 as a gastrin-regulated gene: Role of Rho GTPase and menin.. Gastroenterology 123(1):271-80 PMID: 12105855
