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Published on: November 7, 2025
Multiple tyrosine metabolites are GPR35 agonists.
Huayun Deng1, Haibei Hu, Ye Fang
1Biochemical Technologies, Science and Technology Division , Corning Inc., Corning, NY 14831, United States.
Scientific Reports
|April 24, 2012
Summary
Multiple tyrosine metabolites, including specific carboxylic acid and catechol compounds, activate the GPR35 receptor. This finding identifies new endogenous agonists for GPR35, suggesting potential therapeutic targets for metabolic disorders.
Area of Science:
- Biochemistry
- Pharmacology
- Molecular Biology
Background:
- The endogenous agonists of the GPR35 receptor, such as kynurenic acid, are debated.
- The molecular targets responsible for the nongenomic effects of thyroid hormones remain largely unidentified.
Purpose of the Study:
- To investigate the agonist activity of tyrosine metabolites at the GPR35 receptor.
- To identify novel endogenous ligands for GPR35.
Main Methods:
- Selection of tyrosine metabolism intermediates with carboxylic acid and/or catechol groups.
- Label-free optical biosensor dynamic mass redistribution (DMR) assays in HT-29 cells.
- Confirmatory molecular assays: β-arrestin translocation, ERK phosphorylation, and receptor internalization.
Main Results:
- Several tyrosine metabolites demonstrated agonist activity at GPR35.
- Confirmed GPR35 as a receptor for 5,6-dihydroxyindole-2-carboxylic acid, 3,3',5'-triiodothyronine, 3,3',5-triiodothyronine, gentisate, rosmarinate, and 3-nitrotyrosine.
- Identified multiple tyrosine metabolites as alternative endogenous ligands for GPR35.
Conclusions:
- Multiple tyrosine metabolites function as endogenous agonists of GPR35.
- GPR35 represents a potential druggable target for diseases linked to tyrosine metabolism abnormalities.
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