Systems approach reveals distinct and shared signaling networks of the four PGE2 receptors in T cells
| Autor: | Kjetil Taskén, Albert J. R. Heck, Piero Giansanti, Anna Mari Lone, Aurelien Dugourd, Enio Gjerga, Julio Saez-Rodriguez, Marthe Jøntvedt Jørgensen, Arjen Scholten |
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| Přispěvatelé: | Sub Biomol.Mass Spectrometry & Proteom., Afd Biomol.Mass Spect. and Proteomics, Biomolecular Mass Spectrometry and Proteomics |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Prostaglandin E receptor 3
endocrine system 0303 health sciences Prostaglandin E2 receptor Cancer Cell Biology Biology medicine.disease Biochemistry 03 medical and health sciences 0302 clinical medicine 030220 oncology & carcinogenesis medicine Cancer research lipids (amino acids peptides and proteins) Prostaglandin E2 Receptor Molecular Biology 030304 developmental biology medicine.drug |
| Zdroj: | Science Signaling Science Signaling, 14(703), 1. American Association for the Advancement of Science |
| ISSN: | 1945-0877 |
| Popis: | Prostaglandin E2 (PGE2) promotes an immunosuppressive microenvironment in cancer, partly by signaling through four receptors (EP1, EP2, EP3, and EP4) on T cells. Here, we comprehensively characterized PGE2 signaling networks in helper, cytotoxic, and regulatory T cells using a phosphoproteomics and phosphoflow cytometry approach. We identified ~1500 PGE2-regulated phosphosites and several important EP1–4 signaling nodes, including PKC, CK2, PKA, PI3K, and Src. T cell subtypes exhibited distinct signaling pathways, with the strongest signaling in EP2-stimulated CD8+ cells. EP2 and EP4, both of which signal through Gαs, induced similar signaling outputs, but with distinct kinetics and intensity. Functional predictions from the observed phosphosite changes revealed PGE2 regulation of key cellular and immunological processes. Last, network modeling suggested signal integration between the receptors and a substantial contribution from G protein–independent signaling. This study offers a comprehensive view of the different PGE2-regulated phosphoproteomes in T cell subsets, providing a valuable resource for further research on this physiologically and pathophysiologically important signaling system. |
| Databáze: | OpenAIRE |
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