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

Publication ,  Journal Article
Guo, R; Wan, C-K; Carpenter, JH; Mousallem, T; Boustany, R-MN; Kuan, C-T; Burks, AW; Zhong, X-P
Published in: Proc Natl Acad Sci U S A
August 19, 2008

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.

Duke Scholars

Published In

Proc Natl Acad Sci U S A

DOI

EISSN

1091-6490

Publication Date

August 19, 2008

Volume

105

Issue

33

Start / End Page

11909 / 11914

Location

United States

Related Subject Headings

  • ras Proteins
  • Tissue Culture Techniques
  • Thymus Gland
  • T-Lymphocytes
  • Mitogen-Activated Protein Kinase 3
  • Mitogen-Activated Protein Kinase 1
  • Mice, Knockout
  • Mice, Inbred C57BL
  • Mice
  • Male
 

Citation

APA
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ICMJE
MLA
NLM
Guo, R., Wan, C.-K., Carpenter, J. H., Mousallem, T., Boustany, R.-M., Kuan, C.-T., … Zhong, X.-P. (2008). Synergistic control of T cell development and tumor suppression by diacylglycerol kinase alpha and zeta. Proc Natl Acad Sci U S A, 105(33), 11909–11914. https://doi.org/10.1073/pnas.0711856105
Guo, Rishu, Chi-Keung Wan, Jeffery H. Carpenter, Talal Mousallem, Rose-Mary N. Boustany, Chien-Tsun Kuan, A Wesley Burks, and Xiao-Ping Zhong. “Synergistic control of T cell development and tumor suppression by diacylglycerol kinase alpha and zeta.Proc Natl Acad Sci U S A 105, no. 33 (August 19, 2008): 11909–14. https://doi.org/10.1073/pnas.0711856105.
Guo R, Wan C-K, Carpenter JH, Mousallem T, Boustany R-MN, Kuan C-T, et al. Synergistic control of T cell development and tumor suppression by diacylglycerol kinase alpha and zeta. Proc Natl Acad Sci U S A. 2008 Aug 19;105(33):11909–14.
Guo, Rishu, et al. “Synergistic control of T cell development and tumor suppression by diacylglycerol kinase alpha and zeta.Proc Natl Acad Sci U S A, vol. 105, no. 33, Aug. 2008, pp. 11909–14. Pubmed, doi:10.1073/pnas.0711856105.
Guo R, Wan C-K, Carpenter JH, Mousallem T, Boustany R-MN, Kuan C-T, Burks AW, Zhong X-P. Synergistic control of T cell development and tumor suppression by diacylglycerol kinase alpha and zeta. Proc Natl Acad Sci U S A. 2008 Aug 19;105(33):11909–11914.
Journal cover image

Published In

Proc Natl Acad Sci U S A

DOI

EISSN

1091-6490

Publication Date

August 19, 2008

Volume

105

Issue

33

Start / End Page

11909 / 11914

Location

United States

Related Subject Headings

  • ras Proteins
  • Tissue Culture Techniques
  • Thymus Gland
  • T-Lymphocytes
  • Mitogen-Activated Protein Kinase 3
  • Mitogen-Activated Protein Kinase 1
  • Mice, Knockout
  • Mice, Inbred C57BL
  • Mice
  • Male