Phosphoproteomics-Based Characterization of Prostaglandin E₂ Signaling in T Cells

Prostaglandin E₂ (PGE₂) is a key lipid mediator in health and disease and serves as a crucial link between the immune response and cancer. With the advent of cancer therapies targeting PGE₂ signaling pathways at different levels, there has been increased interest in mapping and understanding the complex and interconnected signaling pathways arising from the four distinct PGE₂ receptors. Here, we review phosphoproteomics studies that have investigated different aspects of PGE₂ signaling in T cells. These studies have elucidated PGE₂'s regulatory effect on T cell receptor signaling and T cell function, the key role of protein kinase A in many PGE₂ signaling pathways, the temporal regulation of PGE₂ signaling, differences in PGE₂ signaling between different T cell subtypes, and finally, the crosstalk between PGE₂ signaling pathways elicited by the four distinct PGE2 receptors present in T cells. SIGNIFICANCE STATEMENT: Through the reviewed studies, we now have a much better understanding of PGE₂'s signaling mechanisms and functional roles in T cells, as well as a solid platform for targeted and functional studies of specific PGE₂-triggered pathways in T cells.