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The importance of the Erk pathway in the development of linker for activation of T cells-mediated autoimmunity.

Publication ,  Journal Article
Fuller, DM; Zhu, M; Koonpaew, S; Nelson, MI; Zhang, W
Published in: J Immunol
October 15, 2012

The ability of the transmembrane adaptor protein linker for activation of T cells (LAT) to regulate T cell development, activation, survival, and homeostasis depends upon phosphorylation of its multiple tyrosine residues. The mutation of tyrosine 136 on LAT abrogates its interaction with phospholipase C-γ1, causing severe ramifications on TCR-mediated signaling. Mice harboring this mutation, LATY136F mice, have significantly impaired thymocyte development; however, they rapidly develop a fatal lymphoproliferative disease marked by the uncontrolled expansion of Th2-skewed CD4(+) T cells, high levels of IgE and IgG1, and autoantibody production. In this study, we assessed the contribution of multiple signaling pathways in LATY136F disease development. The deletion of the critical signaling proteins Gads and RasGRP1 caused a further block in thymocyte development, but, over time, could not prevent CD4(+) T cell hyperproliferation. Also, restoring signaling through the NF-κB and NFAT pathways was unable to halt the development of disease. However, expression of a constitutively active Raf transgene enhanced lymphoproliferation, indicating a role for the Ras-MAPK pathway in LAT-mediated disease.

Duke Scholars

Published In

J Immunol

DOI

EISSN

1550-6606

Publication Date

October 15, 2012

Volume

189

Issue

8

Start / End Page

4005 / 4013

Location

United States

Related Subject Headings

  • raf Kinases
  • Receptors, Antigen, T-Cell
  • Phosphoproteins
  • Mice, Transgenic
  • Mice, Knockout
  • Mice
  • Membrane Proteins
  • MAP Kinase Signaling System
  • Lymphoproliferative Disorders
  • Immunology
 

Citation

APA
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ICMJE
MLA
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Fuller, D. M., Zhu, M., Koonpaew, S., Nelson, M. I., & Zhang, W. (2012). The importance of the Erk pathway in the development of linker for activation of T cells-mediated autoimmunity. J Immunol, 189(8), 4005–4013. https://doi.org/10.4049/jimmunol.1201380
Fuller, Deirdre M., Minghua Zhu, Surapong Koonpaew, Mariana I. Nelson, and Weiguo Zhang. “The importance of the Erk pathway in the development of linker for activation of T cells-mediated autoimmunity.J Immunol 189, no. 8 (October 15, 2012): 4005–13. https://doi.org/10.4049/jimmunol.1201380.
Fuller DM, Zhu M, Koonpaew S, Nelson MI, Zhang W. The importance of the Erk pathway in the development of linker for activation of T cells-mediated autoimmunity. J Immunol. 2012 Oct 15;189(8):4005–13.
Fuller, Deirdre M., et al. “The importance of the Erk pathway in the development of linker for activation of T cells-mediated autoimmunity.J Immunol, vol. 189, no. 8, Oct. 2012, pp. 4005–13. Pubmed, doi:10.4049/jimmunol.1201380.
Fuller DM, Zhu M, Koonpaew S, Nelson MI, Zhang W. The importance of the Erk pathway in the development of linker for activation of T cells-mediated autoimmunity. J Immunol. 2012 Oct 15;189(8):4005–4013.

Published In

J Immunol

DOI

EISSN

1550-6606

Publication Date

October 15, 2012

Volume

189

Issue

8

Start / End Page

4005 / 4013

Location

United States

Related Subject Headings

  • raf Kinases
  • Receptors, Antigen, T-Cell
  • Phosphoproteins
  • Mice, Transgenic
  • Mice, Knockout
  • Mice
  • Membrane Proteins
  • MAP Kinase Signaling System
  • Lymphoproliferative Disorders
  • Immunology