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Regulation of Lipid Signaling by Diacylglycerol Kinases during T Cell Development and Function.

Publication ,  Journal Article
Krishna, S; Zhong, X-P
Published in: Front Immunol
2013

Diacylglycerol (DAG) and phosphatidic acid (PA) are bioactive lipids synthesized when the T cell receptor binds to a cognate peptide-MHC complex. DAG triggers signaling by recruiting Ras guanyl-releasing protein 1, PKCθ, and other effectors, whereas PA binds to effector molecules that include mechanistic target of rapamycin, Src homology region 2 domain-containing phosphatase 1, and Raf1. While DAG-mediated pathways have been shown to play vital roles in T cell development and function, the importance of PA-mediated signals remains less clear. The diacylglycerol kinase (DGK) family of enzymes phosphorylates DAG to produce PA, serving as a molecular switch that regulates the relative levels of these critical second messengers. Two DGK isoforms, α and ζ, are predominantly expressed in T lineage cells and play an important role in conventional αβ T cell development. In mature T cells, the activity of these DGK isoforms aids in the maintenance of self-tolerance by preventing T cell hyper-activation and promoting T cell anergy. In this review, we discuss the roles of DAG-mediated pathways, PA-effectors, and DGKs in T cell development and function. We also highlight recent work that has uncovered previously unappreciated roles for DGK activity, for instance in invariant NKT cell development, anti-tumor and anti-viral CD8 responses, and the directional secretion of soluble effectors.

Duke Scholars

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Published In

Front Immunol

DOI

ISSN

1664-3224

Publication Date

2013

Volume

4

Start / End Page

178

Location

Switzerland

Related Subject Headings

  • 3204 Immunology
  • 3105 Genetics
  • 3101 Biochemistry and cell biology
  • 1108 Medical Microbiology
  • 1107 Immunology
 

Citation

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Krishna, S., & Zhong, X.-P. (2013). Regulation of Lipid Signaling by Diacylglycerol Kinases during T Cell Development and Function. Front Immunol, 4, 178. https://doi.org/10.3389/fimmu.2013.00178
Krishna, Sruti, and Xiao-Ping Zhong. “Regulation of Lipid Signaling by Diacylglycerol Kinases during T Cell Development and Function.Front Immunol 4 (2013): 178. https://doi.org/10.3389/fimmu.2013.00178.
Krishna, Sruti, and Xiao-Ping Zhong. “Regulation of Lipid Signaling by Diacylglycerol Kinases during T Cell Development and Function.Front Immunol, vol. 4, 2013, p. 178. Pubmed, doi:10.3389/fimmu.2013.00178.

Published In

Front Immunol

DOI

ISSN

1664-3224

Publication Date

2013

Volume

4

Start / End Page

178

Location

Switzerland

Related Subject Headings

  • 3204 Immunology
  • 3105 Genetics
  • 3101 Biochemistry and cell biology
  • 1108 Medical Microbiology
  • 1107 Immunology