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Diacylglycerol Kinases (DGKs): Novel Targets for Improving T Cell Activity in Cancer. Front Cell Dev Biol 2016;4:108

Date

11/02/2016

Pubmed ID

27800476

Pubmed Central ID

PMC5065962

DOI

10.3389/fcell.2016.00108

Abstract

Diacylglycerol kinases (DGKs) are a family of enzymes that catalyze the metabolism of diacylglycerol (DAG). Two isoforms of DGK, DGKα, and DGKζ, specifically regulate the pool of DAG that is generated as a second messenger after stimulation of the T cell receptor (TCR). Deletion of either isoform in mouse models results in T cells bearing a hyperresponsive phenotype and enhanced T cell activity against malignancy. Whereas, DGKζ appears to be the dominant isoform in T cells, rationale exists for targeting both isoforms individually or coordinately. Additional work is needed to rigorously identify the molecular changes that result from deletion of DGKs in order to understand how DAG contributes to T cell activation, the effect of DGK inhibition in human T cells, and to rationally develop combined immunotherapeutic strategies that target DGKs.

Author List

Riese MJ, Moon EK, Johnson BD, Albelda SM

Authors

Bryon D. Johnson PhD Professor in the Medicine department at Medical College of Wisconsin
Matthew J. Riese MD, PhD Associate Professor in the Medicine department at Medical College of Wisconsin




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