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Critical Reviews™ in Immunology

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Role of Diacylglycerol Kinases in T Cell Development and Function

Volume 33, Issue 2, 2013, pp. 97-118
DOI: 10.1615/CritRevImmunol.2013006696
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Sruti Krishna
Department of Pediatrics, Division of Allergy and Immunology and Department of Immunology, Duke University Medical Center, Durham, NC
Xiaoping Zhong
Department of Pediatrics, Division of Allergy and Immunology and Department of Immunology, Duke University Medical Center, Durham, NC

ABSTRACT

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.

KEY WORDS: diacylglycerol kinase, phosphatidic acid, signal transduction, T cell receptor
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  3. Chen Shelley S., Hu Zhiming, Zhong Xiao-Ping, Diacylglycerol Kinases in T Cell Tolerance and Effector Function, Frontiers in Cell and Developmental Biology, 4, 2016. Crossref

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  5. Myers Darienne R., Roose Jeroen P., Kinase and Phosphatase Effector Pathways in T Cells, in Encyclopedia of Immunobiology, 2016. Crossref

  6. Riese Matthew J., Moon Edmund K., Johnson Bryon D., Albelda Steven M., Diacylglycerol Kinases (DGKs): Novel Targets for Improving T Cell Activity in Cancer, Frontiers in Cell and Developmental Biology, 4, 2016. Crossref

  7. Wu Jinhong, Shen Shudan, Yang Jialong, Xia Zhenwei, Zhong Xiao-Ping, Moser Muriel, Diacylglycerol Kinase Zeta Positively Controls the Development of iNKT-17 Cells, PLoS ONE, 8, 9, 2013. Crossref

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