Journal
SCIENCE SIGNALING
Volume 8, Issue 374, Pages -Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/scisignal.aaa0974
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Funding
- FPU (Formacion de Profesorado Universitario) fellowship from the Spanish Ministry of Education
- Spanish Anti-Cancer Association
- Madrid regional government
- Madrid regional government [S2010/BMD-2305]
- Spanish Ministry of Economy and Competitivity [BFU2013-47640-P]
- Spanish Ministry of Health (Instituto de Salud Carlos III) [RD12/0036/0059]
- Madrid regional government (IMMUNOTHERCAM) [S2010/BMD-2326]
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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 theRas-extracellular signal-regulated kinase (ERK) and protein kinaseC(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. DGK alpha and DGK zeta 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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