RT Journal Article ID 4981369868ba6016 A1 Krishna , Sruti A1 Zhong, Xiaoping T1 Role of Diacylglycerol Kinases in T Cell Development and Function JF Critical Reviews™ in Immunology JO CRI YR 2013 FD 2013-04-05 VO 33 IS 2 SP 97 OP 118 K1 diacylglycerol kinase K1 phosphatidic acid K1 signal transduction K1 T cell receptor AB Diacylglycerol (DAG), a second messenger generated by phospholipase Cγ1 activity upon engagement of a T-cell receptor, triggers several signaling cascades that play important roles in T cell development and function. A family of enzymes called DAG kinases (DGKs) catalyzes the phosphorylation of DAG to phosphatidic acid, acting as a braking mechanism that terminates DAG-mediated signals. Two DGK isoforms, α and ζ, are expressed predominantly in T cells and synergistically regulate the development of both conventional αβ T cells and invariant natural killer T cells in the thymus. In mature T cells, the activity of these DGK isoforms aids in the maintenance of self-tolerance by preventing T-cell hyperactivation upon T cell receptor stimulation and by promoting T-cell anergy. In CD8 cells, reduced DGK activity is associated with enhanced primary responses against viruses and tumors. Recent work also has established an important role for DGK activity at the immune synapse and identified partners that modulate DGK function. In addition, emerging evidence points to previously unappreciated roles for DGK function in directional secretion and T-cell adhesion. This review describes the multitude of roles played by DGKs in T cell development and function and emphasizes recent advances in the field. PB Begell House LK https://www.dl.begellhouse.com/journals/2ff21abf44b19838,384cd997794a6ddc,4981369868ba6016.html