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.