Diacylglycerol Kinases Put the Brakes on Immune Function

Sci. STKE, 7 August 2007
Vol. 2007, Issue 398, p. pe43
DOI: 10.1126/stke.3982007pe43

Diacylglycerol Kinases Put the Brakes on Immune Function

  1. Binks W. Wattenberg1,* and
  2. Daniel M. Raben2
  1. 1Departments of Medicine, Biochemistry and Molecular Biology, and Pharmacology and Toxicology, University of Louisville, Louisville, KY 40202, USA.
  2. 2Department of Biological Chemistry, The Johns Hopkins School of Medicine, Baltimore, MD 21205, USA.
  1. *Corresponding author: E-mail, b0watt01{at}louisville.edu

Abstract

Diacylglycerol kinases (DGKs) are emerging as key negative regulators of immune function, particularly in T cells. DGKs consume diacylglycerol to produce phosphatidic acid. Because both diacylglycerol and phosphatidic acid are important activators of signaling molecules, DGKs have the potential to modulate a number of signaling pathways, and this certainly seems to be the case in T cell function. Studies of T cell signaling demonstrate that DGKs inhibit T cell receptor signaling and thus may serve an important role in limiting the immune response. Other studies have examined the molecular basis of anergy, a state of T cell unresponsiveness that is an important postdevelopmental control over the immune response to self antigens. Two groups have suggested that DGK activity lies at the heart of the anergic phenotype. In addition, DGK activity may limit the response of macrophages and dendritic cells to intracellular pathogens. An overall picture is emerging in which the capacity of DGKs to modulate membrane signaling lipids is used to keep a tight rein on immune responses.

Citation:

B. W. Wattenberg and D. M. Raben, Diacylglycerol Kinases Put the Brakes on Immune Function. Sci. STKE 2007, pe43 (2007).

FoxO-Dependent Regulation of Diacylglycerol Kinase {alpha} Gene Expression
M. Martinez-Moreno, J. Garcia-Lievana, D. Soutar, P. Torres-Ayuso, E. Andrada, X.-P. Zhong, G. A. Koretzky, I. Merida, and A. Avila-Flores
Mol. Cell. Biol. 32, 4168-4180 (15 October 2012)

SAP-Mediated Inhibition of Diacylglycerol Kinase {alpha} Regulates TCR-Induced Diacylglycerol Signaling
G. Baldanzi, A. Pighini, V. Bettio, E. Rainero, S. Traini, F. Chianale, P. E. Porporato, N. Filigheddu, R. Mesturini, S. Song et al.
J. Immunol. 187, 5941-5951 (1 December 2011)

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882