Phosphoproteomics-Based Characterization of Prostaglandin E2 Signaling in T Cells

Prostaglandin E 2 (PGE 2 ) 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 PGE 2 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 PGE 2 receptors. Here, we review phosphoproteomics studies that have investigated different aspects of PGE 2 signaling in T cells. These studies have elucidated PGE 2 's regulatory effect on T cell receptor signaling and T cell function, the key role of protein kinase A in many PGE 2 signaling pathways, the temporal regulation of PGE 2 signaling, differences in PGE 2 signaling between different T cell subtypes, and finally, the crosstalk between PGE 2 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 PGE 2 's signaling mechanisms and functional roles in T cells, as well as a solid platform for targeted and functional studies of specific PGE 2 -triggered pathways in T cells.