Redundant and specialized roles for diacylglycerol kinases α and ζ in the control of T cell functions

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Sci. Signal.  28 Apr 2015:
Vol. 8, Issue 374, pp. re6
DOI: 10.1126/scisignal.aaa0974

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The diacylglycerol kinases (DGKs) attenuate diacylglycerol (DAG)–mediated signals by catalyzing the conversion of DAG to phosphatidic acid. In T lymphocytes, the antigen-stimulated generation of DAG links signal strength to the intensity and duration of signaling by the Ras–extracellular signal–regulated kinase (ERK) and protein kinase C (PKC)–dependent pathways. The generation of DAG at the plasma membrane of T cells lies at the core of the mechanisms that delimit T cell functions. DGKα and DGKζ are the two main isoforms that are found in T cells, and several approaches define their precise contribution to T cell responses. Each of these isoforms has specialized and redundant functions that limit the intensity of DAG-regulated signals downstream of antigenic stimulation. This ability, which in normal T cells contributes to maintaining homeostasis and function, is exploited by tumors to evade immune surveillance. Modification of DGK activity offers new perspectives for the therapeutic manipulation of T cell functions for treatment of autoimmune pathologies, or for overcoming tumor-induced T cell tolerance. Precise knowledge of the mechanisms that sustain DGK isoform–specific regulation in T lymphocytes is indispensable for the development of new tools for pharmacological intervention.

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