GO:0045744 negative regulation of G protein-coupled receptor signaling pathway: Mechanism, Genes, Functions and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0045744 describes any process that stops, prevents, or reduces the frequency, rate or extent of G protein-coupled receptor (GPCR) signaling.
• GPCR signaling is terminated by a conserved two-step mechanism: agonist-dependent receptor phosphorylation by G protein-coupled receptor kinases (GRKs), followed by arrestin binding that sterically uncouples the receptor from heterotrimeric G proteins.
• Regulators of G-protein-signaling (RGS) proteins act as GTPase-accelerating proteins (GAPs) that shorten the active lifetime of G-alpha subunits, providing a second major negative regulatory layer.
• Negative regulation of GPCR signaling is essential for normal physiology, including growth plate homeostasis through ADGRG6 and IHH signaling and protection against podocyte senescence in diabetic kidney disease through GPR124.
• Dysregulated GPCR negative regulation contributes to human disease, including triple-negative breast cancer metastasis and docetaxel resistance via GPRC5A methylation and inflammation resolution via GPR81-mediated suppression of innate immunity.
• CRISPR knockout, point-mutation, knock-in and overexpression models enable causal dissection of negative regulators such as GRKs, arrestins, RGS proteins and individual GPCRs.
Description
G protein-coupled receptors (GPCRs) form the largest family of cell-surface receptors and transduce signals for hormones, neurotransmitters, metabolites and inflammatory mediators. Because unrestrained GPCR activity can drive pathological signaling, cells deploy dedicated negative regulatory systems that stop, prevent, or reduce the frequency, rate or extent of GPCR signaling, the process formally annotated as GO:0045744. This term captures a biological process rather than a single molecule, encompassing receptor desensitization, G-protein inactivation and downstream feedback control. Mechanistically, the best-characterized negative regulatory module involves agonist-dependent phosphorylation of the activated receptor by G protein-coupled receptor kinases (GRKs), followed by recruitment of arrestins, which sterically uncouple the receptor from heterotrimeric G proteins and promote internalization. A parallel layer is provided by regulators of G-protein-signaling (RGS) proteins, which act as GTPase-accelerating proteins for G-alpha subunits and thereby shorten the duration of the active signaling state. Additional negative regulators can act at the level of the ligand-receptor interface, as shown for the chemokine CCL5, which negatively regulates GPR75 signaling. Understanding GO:0045744 matters because loss of negative regulation is linked to human disease. For example, GPR124 protects against podocyte senescence and injury in diabetic kidney disease, ADGRG6 maintains mouse growth plate homeostasis through IHH signaling, and methylation of GPRC5A promotes liver metastasis and docetaxel resistance through mTOR signaling in triple-negative breast cancer. Conversely, GPR81-mediated suppression of innate immunity reduces liver and pancreatic injury in Toll-like receptor- and inflammasome-mediated inflammation, illustrating that negative regulation of GPCR signaling can be therapeutically beneficial. This article integrates the QuickGO definition with verified PubMed literature to provide a research-grade overview of GO:0045744, its mechanisms, key genes, disease relevance and experimental methods.
negative regulation of G protein-coupled receptor signaling pathway At A Glance
| GO ID | GO:0045744 |
|---|---|
| GO term | negative regulation of G protein-coupled receptor signaling pathway |
| Ontology | biological_process |
| Definition | Any process that stops, prevents, or reduces the frequency, rate or extent of G protein-coupled receptor signaling pathway. |
| Synonyms | down regulation of G-protein coupled receptor protein signaling pathway; inhibition of G-protein coupled receptor protein signaling pathway; negative regulation of GPCR protein signaling pathway; negative regulation of G-protein coupled receptor protein signalling pathway |
| Major function | Termination or dampening of GPCR-initiated signals via GRK-mediated phosphorylation, arrestin recruitment, RGS-mediated G-alpha GTPase acceleration and ligand-dependent negative modulation |
| Biological context | Receptor desensitization, G-protein inactivation, feedback control of hormone, neurotransmitter, metabolite and inflammatory signaling |
| Disease relevance | Diabetic kidney disease, growth plate disorders, triple-negative breast cancer metastasis and docetaxel resistance, inflammatory liver and pancreatic injury |
| Experimental models | CRISPR knockout, point-mutation, knock-in and overexpression cell and animal models targeting GRKs, arrestins, RGS proteins and individual GPCRs |
What Is GO:0045744?
GO:0045744, negative regulation of G protein-coupled receptor signaling pathway, is a biological process defined by QuickGO as any process that stops, prevents, or reduces the frequency, rate or extent of G protein-coupled receptor signaling pathway. In practice, this includes molecular events such as receptor phosphorylation by GRKs, arrestin recruitment and receptor uncoupling from G proteins, GTPase acceleration on G-alpha subunits by RGS proteins, and ligand-dependent negative modulation of specific GPCRs such as CCL5 acting on GPR75. The term is a negative regulatory node that sits upstream of, or parallel to, the core GPCR signaling cascade and ensures that receptor-initiated signals are appropriately terminated or dampened.
Why Is negative regulation of G protein-coupled receptor signaling pathway Important in Cell Biology?
Negative regulation of GPCR signaling is a central homeostatic mechanism that prevents excessive or prolonged receptor activation. Without it, cells would be unable to desensitize to persistent stimuli, and tissues would be vulnerable to pathological signaling. The importance of GO:0045744 is underscored by its involvement in diverse physiological and disease contexts: GPR124 protects against podocyte senescence and injury in diabetic kidney disease, ADGRG6 maintains mouse growth plate homeostasis through IHH signaling, GPRC5A methylation promotes liver metastasis and docetaxel resistance through mTOR signaling in triple-negative breast cancer, and GPR81-mediated suppression of innate immunity reduces liver and pancreatic injury in Toll-like receptor- and inflammasome-mediated inflammation. In addition, the chemokine CCL5 acts as a negative regulator of GPR75, illustrating ligand-level control of GPCR signaling. Together, these findings establish GO:0045744 as a process of broad biomedical significance and a rich source of therapeutic targets.
• Prevents prolonged or excessive GPCR signaling by promoting receptor desensitization and uncoupling from G proteins.
• Provides a general mechanism for terminating hormone, neurotransmitter, metabolite and inflammatory signals.
• Protects against diabetic kidney disease through GPR124-mediated protection of podocytes from senescence and injury.
• Maintains skeletal growth plate homeostasis via ADGRG6 regulation of IHH signaling.
• Limits tumor progression and chemoresistance, as shown for GPRC5A methylation in triple-negative breast cancer.
• Dampens innate immunity and inflammation through GPR81, reducing liver and pancreatic injury.
• Enables ligand-level negative control of GPCRs, exemplified by CCL5 as a negative regulator of GPR75.
• Informs drug discovery by identifying GRKs, arrestins and RGS proteins as tractable nodes for modulating GPCR activity.
• Supports precision medicine by linking specific GPCR negative regulators to distinct disease phenotypes.
• Provides a conceptual framework for CRISPR-based functional genomics of GPCR regulatory networks.
What Happens During negative regulation of G protein-coupled receptor signaling pathway?
Agonist-dependent receptor phosphorylation by GRKs
In simple terms: When a receptor is active, specialized kinases tag it with phosphate groups to start shutting it down.
The first step in negative regulation of GPCR signaling is agonist-dependent phosphorylation of the activated receptor by G protein-coupled receptor kinases (GRKs). This phosphorylation occurs on serine and threonine residues in the receptor's intracellular loops and C-terminal tail, creating a high-affinity binding site for arrestin proteins. GRK-mediated phosphorylation is a key determinant of the rate and extent of receptor desensitization and is conserved across many GPCRs.
Arrestin recruitment and receptor uncoupling
In simple terms: Arrestin proteins bind the phosphorylated receptor and physically block it from activating G proteins.
Following GRK-mediated phosphorylation, arrestins bind the receptor and sterically uncouple it from heterotrimeric G proteins, thereby stopping downstream G-protein activation. Arrestin binding also promotes receptor internalization, which can lead to receptor recycling or degradation, further reducing the frequency and extent of GPCR signaling. This feedback regulation by GRKs and arrestins is a central mechanism of GO:0045744.
RGS-mediated GTPase acceleration on G-alpha subunits
In simple terms: RGS proteins act as timers that switch off the active G-alpha subunit faster.
Regulators of G-protein-signaling (RGS) proteins function as negative modulators of GPCR signaling by acting as GTPase-accelerating proteins (GAPs) for G-alpha subunits. By accelerating GTP hydrolysis, RGS proteins shorten the lifetime of the active GTP-bound G-alpha subunit, thereby reducing the duration and amplitude of downstream signaling. This provides a complementary negative regulatory layer that operates downstream of receptor activation.
Ligand-dependent negative modulation of specific GPCRs
In simple terms: Some molecules can directly dampen a receptor's activity by binding to it or its partner.
Negative regulation of GPCR signaling can also occur at the level of the ligand-receptor interface. For example, the chemokine CCL5 has been identified as a negative regulator of GPR75, uncovering a ligand-dependent mechanism that modulates GPR75 signaling. Such ligand-level control adds specificity to GO:0045744 and can be exploited to tune individual GPCR pathways.
Physiological consequences of negative regulation
In simple terms: Shutting down GPCR signals at the right time keeps tissues healthy.
Proper negative regulation of GPCR signaling is required for tissue homeostasis. GPR124 protects against podocyte senescence and injury in diabetic kidney disease, and ADGRG6 maintains mouse growth plate homeostasis through IHH signaling. In inflammation, GPR81-mediated suppression of innate immunity reduces liver and pancreatic injury in Toll-like receptor- and inflammasome-mediated inflammation. These examples illustrate that GO:0045744 is not merely a molecular brake but a determinant of organ-level physiology.
Key Genes Involved in GO:0045744 negative regulation of G protein-coupled receptor signaling pathway
The following genes and proteins are experimentally implicated in negative regulation of GPCR signaling, either as core machinery (GRKs, arrestins, RGS proteins) or as specific GPCRs whose negative regulation has been linked to disease biology.
| Gene | Major Role | Research Relevance |
|---|---|---|
| GRK2 | Agonist-dependent phosphorylation of activated GPCRs, initiating desensitization | Core negative regulator; target for modulating GPCR signaling in disease models |
| GRK3 | Phosphorylation of activated GPCRs, contributing to arrestin recruitment | Context-dependent negative regulator of GPCR signaling |
| GRK5 | Phosphorylation of activated GPCRs, promoting desensitization | Candidate for CRISPR knockout studies of GPCR desensitization |
| GRK6 | Phosphorylation of activated GPCRs, contributing to negative regulation | Potential target for tuning GPCR signaling in immune and neuronal cells |
| ARRB1 | Arrestin recruitment to phosphorylated GPCRs, uncoupling from G proteins | Central effector of GPCR desensitization and internalization |
| ARRB2 | Arrestin recruitment to phosphorylated GPCRs, uncoupling from G proteins | Key node for feedback regulation of GPCR signaling |
| RGS1 | GTPase-accelerating protein for G-alpha subunits | Negative modulator of GPCR signaling; candidate for functional genomics |
| RGS2 | GTPase-accelerating protein for G-alpha subunits | Negative modulator of GPCR signaling in cardiovascular and neuronal contexts |
| RGS4 | GTPase-accelerating protein for G-alpha subunits | Negative modulator of GPCR signaling; relevant to neuropsychiatric research |
| RGS10 | GTPase-accelerating protein for G-alpha subunits | Negative modulator of GPCR signaling in immune and inflammatory pathways |
| GPR124 | Protects against podocyte senescence and injury in diabetic kidney disease | Disease-relevant GPCR whose negative regulation supports kidney homeostasis |
| ADGRG6 | Maintains mouse growth plate homeostasis through IHH signaling | Adhesion GPCR linked to skeletal development and growth plate biology |
| GPRC5A | Methylation promotes liver metastasis and docetaxel resistance via mTOR signaling in triple-negative breast cancer | Epigenetically regulated GPCR with oncogenic roles |
| GPR81 | Mediates lactate-dependent suppression of innate immunity, reducing liver and pancreatic injury | Metabolite-sensing GPCR with anti-inflammatory function |
| GPR75 | Negatively regulated by the chemokine CCL5 | GPCR with ligand-dependent negative regulation; relevant to chemokine biology |
| GPR25 | Promotes formation of lung and liver tissue-resident memory CD8 T cells | GPCR involved in T cell residency; context for negative regulation studies |
How Is negative regulation of G protein-coupled receptor signaling pathway Regulated?
Negative regulation of GPCR signaling is itself subject to regulation at multiple levels. GRK-mediated phosphorylation and arrestin recruitment constitute a feedback loop that is triggered by agonist occupancy and can be modulated by receptor conformation and cellular context. RGS proteins provide a parallel regulatory layer by accelerating GTP hydrolysis on G-alpha subunits, and their expression and activity can be tuned by signaling inputs. In disease contexts, epigenetic mechanisms can alter the expression of GPCRs themselves, as shown for GPRC5A methylation in triple-negative breast cancer, which activates mTOR signaling and promotes liver metastasis and docetaxel resistance. In addition, ligand availability can regulate GPCR activity, exemplified by CCL5 acting as a negative regulator of GPR75. These layers collectively determine the set point of GPCR signaling and are relevant to therapeutic modulation of GO:0045744.
negative regulation of G protein-coupled receptor signaling pathway and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| GPR124 | Diabetic kidney disease; podocyte senescence and injury | Podocyte-specific knockout or overexpression in diabetic mouse models |
| ADGRG6 | Growth plate homeostasis and skeletal development | Chondrocyte-specific knockout or knock-in in mouse growth plates |
| GPRC5A | Triple-negative breast cancer liver metastasis and docetaxel resistance | CRISPR knockout or methylation-edited breast cancer cell lines and xenografts |
| GPR81 | Toll-like receptor- and inflammasome-mediated liver and pancreatic injury | Knockout mice or hepatocyte/pancreatic cell models with GPR81 deletion |
| GPR75 | Chemokine CCL5-dependent negative regulation | GPR75 knockout or point-mutation cell lines treated with CCL5 |
Diabetic kidney disease and podocyte injury
GPR124 protects against podocyte senescence and injury in diabetic kidney disease, indicating that GPCR-mediated protective signaling is important for maintaining glomerular integrity. Negative regulation of GPCR signaling pathways may influence the balance between protective and injurious signaling in podocytes, making GPR124 and its regulatory network candidate targets for kidney disease research.
Skeletal growth plate disorders
ADGRG6 maintains mouse growth plate homeostasis through IHH signaling, linking an adhesion GPCR to skeletal development. Dysregulation of GPCR signaling in chondrocytes can disrupt growth plate architecture, and negative regulatory mechanisms that tune ADGRG6 activity are therefore relevant to growth disorders.
Triple-negative breast cancer metastasis and chemoresistance
Methylation of GPRC5A promotes liver metastasis and docetaxel resistance through activation of mTOR signaling in triple-negative breast cancer. This illustrates how epigenetic silencing or activation of a GPCR can bypass normal negative regulatory control and drive aggressive disease phenotypes.
Inflammatory liver and pancreatic injury
Lactate reduces liver and pancreatic injury in Toll-like receptor- and inflammasome-mediated inflammation via GPR81-mediated suppression of innate immunity. This demonstrates that GPCR-initiated negative regulation of inflammatory signaling can be protective, and that GPR81 is a key node in metabolic-inflammatory crosstalk.
From negative regulation of G protein-coupled receptor signaling pathway-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does loss of a GRK or arrestin enhance GPCR signaling? | CRISPR knockout of GRK2/3/5/6 or ARRB1/2 in receptor-expressing cell lines |
| Does a point mutation in a GPCR alter its desensitization? | CRISPR point-mutation knock-in of phosphorylation-site mutants in the receptor C-terminal tail |
| Does a tagged GPCR interact with arrestins or RGS proteins? | Tagged knock-in of the GPCR with a fluorescent or affinity tag for interaction studies |
| Does overexpression of an RGS protein reduce GPCR signaling? | Overexpression of RGS1/2/4/10 in GPCR reporter cell lines |
| Does GPR124 protect podocytes in diabetic kidney disease? | Podocyte-specific knockout or overexpression in diabetic mouse models |
| Does GPRC5A methylation drive docetaxel resistance? | CRISPR knockout or epigenetic editing of GPRC5A in triple-negative breast cancer cells |
How to Study the negative regulation of G protein-coupled receptor signaling pathway Process
| Method | What It Measures | Typical Application |
|---|---|---|
| CRISPR knockout | Loss-of-function effects of negative regulators such as GRKs, arrestins and RGS proteins | Identifying which negative regulators control a given GPCR pathway |
| CRISPR point mutation | Effect of specific phosphorylation or binding-site residues on receptor desensitization | Dissecting GRK phosphorylation site function in GPCR C-terminal tails |
| Tagged knock-in | Localization and interaction dynamics of GPCRs, arrestins and RGS proteins | Imaging receptor-arrestin complexes and RGS recruitment |
| Overexpression | Gain-of-function effects of negative regulators on GPCR signaling amplitude | Testing whether RGS proteins suppress GPCR signaling in reporter cells |
| RNA sequencing | Transcriptional changes downstream of GPCR negative regulation | Identifying mTOR-dependent gene programs in GPRC5A-driven breast cancer |
| Proteomics | Protein interaction networks of arrestins, GRKs and RGS proteins | Mapping context-dependent GPCR regulatory complexes |
| cAMP/calcium assays | Real-time GPCR signaling output | Quantifying desensitization kinetics in knockout or mutant cells |
| In vivo knockout models | Organ-level consequences of losing GPCR negative regulation | Modeling diabetic kidney disease, growth plate disorders and inflammatory injury |
CRISPR knockout and point-mutation screens
CRISPR knockout and point-mutation approaches enable systematic interrogation of negative regulators of GPCR signaling. Knockout of GRKs, arrestins or RGS proteins can reveal their contribution to receptor desensitization and downstream signaling. Point-mutation knock-in of phosphorylation sites in GPCR C-terminal tails can dissect the contribution of individual phospho-acceptor residues to arrestin recruitment and receptor uncoupling.
Transcriptomic and proteomic profiling
RNA sequencing and proteomics can quantify changes in GPCR signaling networks following perturbation of negative regulators. For example, GPRC5A methylation activates mTOR signaling in triple-negative breast cancer, and transcriptomic profiling can identify downstream effectors of this axis. Proteomic analysis of arrestin and RGS interactomes can reveal context-dependent binding partners.
Functional signaling assays
GPCR signaling can be measured using cAMP, calcium, or reporter-based assays in cells with engineered loss or gain of negative regulators. Such assays are used to quantify the effect of GRK or arrestin knockout on receptor desensitization kinetics. RGS protein overexpression or knockout can be used to measure changes in G-alpha GTP hydrolysis and downstream signaling amplitude.
In vivo disease models
Mouse models with tissue-specific manipulation of GPCR negative regulators are used to link molecular mechanisms to disease phenotypes. Podocyte-specific GPR124 models have been used to study diabetic kidney disease, chondrocyte-specific ADGRG6 models to study growth plate homeostasis, and GPR81 knockout models to study inflammatory liver and pancreatic injury.
How CRISPR Can Be Used to Study GO:0045744 negative regulation of G protein-coupled receptor signaling pathway
Knockout
CRISPR knockout of negative regulators such as GRKs, arrestins or RGS proteins is used to test whether loss of these proteins enhances GPCR signaling. For example, knocking out GRK2 or ARRB1/2 in receptor-expressing cells can reveal their contribution to receptor desensitization. Knockout of RGS proteins can increase the amplitude and duration of G-alpha signaling. In disease models, knockout of GPR124 in podocytes can test its protective role in diabetic kidney disease.
Point Mutation
CRISPR point-mutation knock-in enables precise modification of phosphorylation sites or binding motifs in GPCRs and their regulators. Mutating serine and threonine residues in a GPCR C-terminal tail can prevent GRK-mediated phosphorylation and arrestin recruitment, thereby impairing negative regulation. Point mutations in RGS proteins can disrupt their GTPase-accelerating activity and prolong G-alpha signaling.
Knock-in
Tagged knock-in of GPCRs, arrestins or RGS proteins allows real-time visualization and interaction studies. Fluorescent or affinity tags can be inserted into endogenous loci to track receptor trafficking, arrestin recruitment and RGS localization without overexpression artifacts. Knock-in of disease-associated variants can also model how specific mutations alter negative regulation of GPCR signaling.
Overexpression
CRISPR-based overexpression or cDNA overexpression of negative regulators such as RGS proteins can suppress GPCR signaling and test therapeutic hypotheses. Overexpressing RGS1/2/4/10 can reduce G-alpha signaling amplitude in reporter cells. Overexpression of protective GPCRs such as GPR124 can be used to test whether enhancing their function mitigates podocyte injury in diabetic kidney disease.
How EDITGENE Supports negative regulation of G protein-coupled receptor signaling pathway Research
Researchers studying negative regulation of G protein-coupled receptor signaling pathway-related genes often need to determine whether a candidate gene is causally involved in receptor desensitization, G-protein inactivation or disease phenotypes. EDITGENE provides end-to-end CRISPR services that enable precise, reproducible interrogation of these mechanisms in relevant cell and animal models.
Contact EDITGENE today to design your custom CRISPR model for negative regulation of G protein-coupled receptor signaling pathway research.
Frequently Asked Questions About negative regulation of G protein-coupled receptor signaling pathway
What is GO:0045744?
GO:0045744 is the Gene Ontology term for negative regulation of G protein-coupled receptor signaling pathway, defined as any process that stops, prevents, or reduces the frequency, rate or extent of GPCR signaling.
What is negative regulation of G protein-coupled receptor signaling pathway?
It is the set of cellular mechanisms that terminate or dampen GPCR-initiated signals, including GRK-mediated receptor phosphorylation, arrestin recruitment, receptor uncoupling from G proteins and RGS-mediated GTPase acceleration.
What genes are involved in negative regulation of GPCR signaling?
Key genes include GRKs (GRK2, GRK3, GRK5, GRK6), arrestins (ARRB1, ARRB2) and RGS proteins (RGS1, RGS2, RGS4, RGS10), as well as specific GPCRs such as GPR124, ADGRG6, GPRC5A, GPR81 and GPR75.
How do GRKs and arrestins negatively regulate GPCR signaling?
GRKs phosphorylate activated GPCRs, creating binding sites for arrestins, which then sterically uncouple the receptor from heterotrimeric G proteins and promote internalization, thereby reducing signaling.
What is the role of RGS proteins in GPCR negative regulation?
RGS proteins act as GTPase-accelerating proteins for G-alpha subunits, shortening the lifetime of the active GTP-bound state and thereby reducing the duration and amplitude of GPCR signaling.
Which diseases are linked to defective negative regulation of GPCR signaling?
Diabetic kidney disease, growth plate disorders, triple-negative breast cancer metastasis and docetaxel resistance, and inflammatory liver and pancreatic injury have been linked to altered GPCR negative regulation.
How can CRISPR be used to study negative regulation of GPCR signaling?
CRISPR knockout, point-mutation, knock-in and overexpression models can be used to test the causal role of GRKs, arrestins, RGS proteins and individual GPCRs in receptor desensitization and disease phenotypes.
What experimental models are suitable for studying GO:0045744?
Suitable models include knockout and knock-in cell lines for GRKs, arrestins and RGS proteins, reporter cell lines for cAMP or calcium signaling, and tissue-specific mouse models such as podocyte-specific GPR124 or chondrocyte-specific ADGRG6 models.
Can GPCR negative regulation be therapeutically targeted?
Yes, modulating GRKs, arrestins or RGS proteins could tune GPCR signaling in disease; for example, enhancing GPR124 function may protect podocytes in diabetic kidney disease, and GPR81-mediated suppression of innate immunity reduces inflammatory injury.
What methods are used to measure negative regulation of GPCR signaling?
Common methods include cAMP and calcium assays, receptor phosphorylation and arrestin recruitment assays, RNA sequencing, proteomics and CRISPR-based functional screens.
Conclusion
GO:0045744, negative regulation of G protein-coupled receptor signaling pathway, is a fundamental biological process that ensures appropriate termination and dampening of GPCR-initiated signals. Its core mechanisms include GRK-mediated receptor phosphorylation, arrestin recruitment and uncoupling from G proteins, and RGS-mediated GTPase acceleration. These mechanisms are critical for normal physiology and are implicated in diverse diseases, including diabetic kidney disease, growth plate disorders, triple-negative breast cancer and inflammatory injury. CRISPR-based knockout, point-mutation, knock-in and overexpression models provide powerful tools to dissect the causal roles of GRKs, arrestins, RGS proteins and individual GPCRs in this process. By combining precise genome editing with functional signaling assays, transcriptomics and proteomics, researchers can accelerate the translation of GPCR negative regulation biology into therapeutic strategies.
References
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- 3. Ou X et al.. 2024. Methylation of GPRC5A promotes liver metastasis and docetaxel resistance through activating mTOR signaling pathway in triple negative breast cancer.. Drug Resist Updat 73:101063 PMID: 38335844
- 4. Black JB et al.. 2016. Feedback regulation of G protein-coupled receptor signaling by GRKs and arrestins.. Semin Cell Dev Biol 50:95-104 PMID: 26773211
- 5. Hoque R et al.. 2014. Lactate reduces liver and pancreatic injury in Toll-like receptor- and inflammasome-mediated inflammation via GPR81-mediated suppression of innate immunity.. Gastroenterology 146(7):1763-74 PMID: 24657625
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