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Disruption of Mekk2 in mice reveals an unexpected role for MEKK2 in modulating T-cell receptor signal transduction.

Publication ,  Journal Article
Guo, Z; Clydesdale, G; Cheng, J; Kim, K; Gan, L; McConkey, DJ; Ullrich, SE; Zhuang, Y; Su, B
Published in: Mol Cell Biol
August 2002

MEKK2 is a member of the mitogen-activated protein kinase (MAPK) kinase kinase gene family involved in regulating multiple MAPK signaling pathways. To elucidate the in vivo function of MEKK2, we generated mice carrying a targeted mutation in the Mekk2 locus. Mekk2(-/-) mice are viable and fertile. Major subsets of thymic and spleen T cells in Mekk2-deficient mice were indistinguishable from those in wild-type mice. B-cell development appeared to proceed similarly in the bone marrow of Mekk2-deficient and wild-type mice. However, Mekk2(-/-) T-cell proliferation was augmented in response to anti-CD3 monoclonal antibody (MAb) stimulation, and these T cells produced more interleukin 2 and gamma interferon than did the wild-type T cells, suggesting that MEKK2 may be involved in controlling the strength of T-cell receptor (TCR) signaling. Consistently, Mekk2(-/-) thymocytes were more susceptible than wild-type thymocytes to anti-CD3 MAb-induced cell death. Furthermore, TCR-mediated c-Jun N-terminal kinase activation was not blocked but moderately enhanced in Mekk2(-/-) T cells. Neither extracellular signal-regulated kinase nor p38 MAPK activation was affected in Mekk2(-/-) T cells. In conclusion, we found that MEKK2 may be required for controlling the strength of TCR/CD3 signaling.

Duke Scholars

Published In

Mol Cell Biol

DOI

ISSN

0270-7306

Publication Date

August 2002

Volume

22

Issue

16

Start / End Page

5761 / 5768

Location

United States

Related Subject Headings

  • Ultraviolet Rays
  • Thymus Gland
  • T-Lymphocytes
  • Signal Transduction
  • Recombination, Genetic
  • Receptors, Antigen, T-Cell
  • Mutation
  • Mitogen-Activated Protein Kinases
  • Mice, Knockout
  • Mice
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Guo, Z., Clydesdale, G., Cheng, J., Kim, K., Gan, L., McConkey, D. J., … Su, B. (2002). Disruption of Mekk2 in mice reveals an unexpected role for MEKK2 in modulating T-cell receptor signal transduction. Mol Cell Biol, 22(16), 5761–5768. https://doi.org/10.1128/MCB.22.16.5761-5768.2002
Guo, Zijian, Gavin Clydesdale, Jinke Cheng, Kihwan Kim, Lin Gan, David J. McConkey, Stephen E. Ullrich, Yuan Zhuang, and Bing Su. “Disruption of Mekk2 in mice reveals an unexpected role for MEKK2 in modulating T-cell receptor signal transduction.Mol Cell Biol 22, no. 16 (August 2002): 5761–68. https://doi.org/10.1128/MCB.22.16.5761-5768.2002.
Guo Z, Clydesdale G, Cheng J, Kim K, Gan L, McConkey DJ, et al. Disruption of Mekk2 in mice reveals an unexpected role for MEKK2 in modulating T-cell receptor signal transduction. Mol Cell Biol. 2002 Aug;22(16):5761–8.
Guo, Zijian, et al. “Disruption of Mekk2 in mice reveals an unexpected role for MEKK2 in modulating T-cell receptor signal transduction.Mol Cell Biol, vol. 22, no. 16, Aug. 2002, pp. 5761–68. Pubmed, doi:10.1128/MCB.22.16.5761-5768.2002.
Guo Z, Clydesdale G, Cheng J, Kim K, Gan L, McConkey DJ, Ullrich SE, Zhuang Y, Su B. Disruption of Mekk2 in mice reveals an unexpected role for MEKK2 in modulating T-cell receptor signal transduction. Mol Cell Biol. 2002 Aug;22(16):5761–5768.

Published In

Mol Cell Biol

DOI

ISSN

0270-7306

Publication Date

August 2002

Volume

22

Issue

16

Start / End Page

5761 / 5768

Location

United States

Related Subject Headings

  • Ultraviolet Rays
  • Thymus Gland
  • T-Lymphocytes
  • Signal Transduction
  • Recombination, Genetic
  • Receptors, Antigen, T-Cell
  • Mutation
  • Mitogen-Activated Protein Kinases
  • Mice, Knockout
  • Mice