SPC/LPC/proton-sensor GPCR Assays
Background of SPC/LPC/proton-sensor Receptors
1-1-1-1-61 SPC-LPC-proton-sensor GPCR Assays-The group of SPC/LPC/proton-sensor receptors consists of the four receptors GPR4, GPR65, GPR68, and GPR132. These receptors are acidification sensors in cells, a feature attributable to the presence of critical histidine residues. These receptors are known to play a role in various areas of tumor biology, cardiovascular physiology, and asthma.
Fig.1 Lonotropic and metabotropic proton-sensing receptors. (Aoki, 2014)
Distributions and Functions of SPC/LPC/proton-sensor Receptors
GPR4 is involved in the tube formation of vascular endothelial cells, suggesting the roles it plays in the angiogenesis, tumor growth, and metastasis of cancers. GPR65 receptors are distributed throughout the immune system, enhancing glucocorticoid-mediated apoptosis and regulating the viability of allergen-elicited BALF eosinophils. GPR68 receptors are widely expressed in the spleen, brain, thyroid cells, heart, lung, placenta, testis, and immune cells, which participate in vascular physiology, cancer emerg, brain ischemia, etc. GPR132 is responsible for hepatobiliary bile salt, cholesterol, and phospholipid homeostasis, macrophage-mediated neutrophil clearance, and promoting cell cycle arrest of tumors.
Subtypes and Mechanisms of SPC/LPC/proton-sensor Receptors
GPR4, GPR65, GPR68, and GPR132 receptors are belonging to class A orphan GPCRs activated by protons. Their signal transduction mechanisms are different.
| Receptor | Gene | Mechanism | Agonists | Antagonists |
| GPR4 receptor | GRP4 |
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| GPR65 receptor | GPR65 |
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| GPR68 receptor | GPR68 |
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| GPR132 receptor | GPR132 |
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Assay List of SPC/LPC/Proton-sensor Receptor
Creative Biolabs can provide a range of assays of SPC/LPC/Proton-sensor receptors. You can choose the assay in the list or contact us for more information:
Published Data
| Paper Title | Increased proton-sensing receptor GPR4 signaling promotes colorectal cancer progression by activating the hippo pathway |
| Journal | EBioMedicine |
| Published | 2019 |
| Abstract | There are no effective therapeutic strategies for late-stage and metastatic colorectal cancer (CRC) patients. Acidity is one characteristic of the tumor microenvironment. This study aimed to investigate the cancer cell response to an acidic environment, especially in colorectal cancer. They analyzed the GEO and TCGA datasets to demonstrate proton sensor receptor expression. They confirmed the expression of GPR4 in CRC specimens via western blotting and immunohistochemistry (IHC). Both in vitro and in vivo experiments were applied to investigate the role of GPR4 in CRC progression. Also, they aimed to reveal the underlying molecular mechanisms of GPR4, using pharmacological intervention, immunofluorescence, and gene set enrichment analyses. |
| Result |
They found that GPR4 was upregulated in CRC samples. The high expression of GPR4 was found to be correlated with late-stage tumors and poor overall survival in patients. In addition, they utilized the loss-of-function assays to prove that GPR4 promoted CRC carcinogenesis and metastatic ability. They have explained the molecular mechanisms of GPR4 that GPR4 was activated by extracellular protons in the tumor microenvironment and enhanced RhoA activation and F-actin rearrangement, resulting in LATS activity inhibition, YAP1 nuclear translocation, and oncogene transcription, revealing the novel roles of GPR4 in CRC progression. The study provided us with a new perspective that the GPR4 might be a new therapeutic target for CRC treatment.
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Fig.2 Activated GPR4 triggers hippo pathway. (Yu, 2019)
References
- Aoki, H.; et al. Ionotropic and metabotropic proton-sensing receptors involved in airway inflammation in allergic asthma. Mediators of Inflammation. 2014, 2014: 1-8.
- Yu, M.; et al. Increased proton-sensing receptor GPR4 signaling promotes colorectal cancer progression by activating the hippo pathway. EBioMedicine. 2019, 48: 264-276.
