Synergistic control of T cell development and tumor suppression by diacylglycerol kinase alpha and zeta.

Journal Article

Diacylglycerol (DAG) kinases (DGKs) are a family of enzymes that convert DAG to phosphatidic acid (PA), the physiologic functions of which have been poorly defined. We report here that DGK alpha and zeta synergistically promote T cell maturation in the thymus. Absence of both DGKalpha and zeta (DGKalpha(-/-)zeta(-/-)) results in a severe decrease in the number of CD4(+)CD8(-) and CD4(-)CD8(+) single-positive thymocytes correlating with increased DAG-mediated signaling. Positive selection, but not negative selection, is impaired in DGKalpha(-/-)zeta(-/-) mice. The developmental blockage in DGKalpha(-/-)zeta(-/-) mice can be partially overcome by treatment with PA. Furthermore, decreased DGK activity also promotes thymic lymphomagenesis accompanying elevated Ras and Erk1/2 activation. Our data demonstrate a synergistic and critical role of DGK isoforms in T cell development and tumor suppression, and indicate that DGKs not only terminate DAG signaling but also initiate PA signaling in thymocytes to promote positive selection.

Full Text

Duke Authors

Cited Authors

  • Guo, R; Wan, C-K; Carpenter, JH; Mousallem, T; Boustany, R-MN; Kuan, C-T; Burks, AW; Zhong, X-P

Published Date

  • August 19, 2008

Published In

Volume / Issue

  • 105 / 33

Start / End Page

  • 11909 - 11914

PubMed ID

  • 18689679

Electronic International Standard Serial Number (EISSN)

  • 1091-6490

Digital Object Identifier (DOI)

  • 10.1073/pnas.0711856105

Language

  • eng

Conference Location

  • United States