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Tyrosine phosphorylation-independent regulation of lipopolysaccharide-mediated response by the transmembrane adaptor protein LAB.

Publication ,  Journal Article
Zhu, M; Fuller, DM; Ou-Yang, C-W; Sullivan, SA; Zhang, W
Published in: J Immunol
March 15, 2012

Linker for activation of B cells (LAB)/non-T cell activation linker is a transmembrane adaptor protein that functions in immunoreceptor-mediated signaling. Published studies have shown that LAB has both positive and negative roles in regulating TCR and high-affinity Fc receptor-mediated signaling and cellular function. In this study, we showed that LAB was also expressed in dendritic cells and that LAB deficiency affected LPS-mediated signaling and cytokine production. LPS-mediated MAPK activation was enhanced in LAB(-/-) bone marrow-derived dendritic cells. These bone marrow-derived dendritic cells also produced more TNF-α, IL-6, and IL-10 than wild-type cells. Moreover, LAB(-/-) mice were hyperresponsive to LPS-induced septic shock. These data indicated that LAB has a negative role in LPS-mediated responses. By using LAB knockin mice, which harbor mutations at five membrane-distal tyrosines, we further showed that, in contrast to its role in immunoreceptor-mediated signaling, LAB function in LPS-mediated signaling pathway did not depend on its tyrosine phosphorylation. Our study suggested a novel mechanism by which LAB functions in the regulation of innate immunity.

Duke Scholars

Published In

J Immunol

DOI

EISSN

1550-6606

Publication Date

March 15, 2012

Volume

188

Issue

6

Start / End Page

2733 / 2741

Location

United States

Related Subject Headings

  • Tyrosine
  • Signal Transduction
  • Real-Time Polymerase Chain Reaction
  • Phosphorylation
  • Mice, Knockout
  • Mice
  • Lipopolysaccharides
  • Immunoprecipitation
  • Immunology
  • Immunity, Innate
 

Citation

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Zhu, M., Fuller, D. M., Ou-Yang, C.-W., Sullivan, S. A., & Zhang, W. (2012). Tyrosine phosphorylation-independent regulation of lipopolysaccharide-mediated response by the transmembrane adaptor protein LAB. J Immunol, 188(6), 2733–2741. https://doi.org/10.4049/jimmunol.1101581
Zhu, Minghua, Deirdre M. Fuller, Chih-wen Ou-Yang, Sarah A. Sullivan, and Weiguo Zhang. “Tyrosine phosphorylation-independent regulation of lipopolysaccharide-mediated response by the transmembrane adaptor protein LAB.J Immunol 188, no. 6 (March 15, 2012): 2733–41. https://doi.org/10.4049/jimmunol.1101581.
Zhu M, Fuller DM, Ou-Yang C-W, Sullivan SA, Zhang W. Tyrosine phosphorylation-independent regulation of lipopolysaccharide-mediated response by the transmembrane adaptor protein LAB. J Immunol. 2012 Mar 15;188(6):2733–41.
Zhu, Minghua, et al. “Tyrosine phosphorylation-independent regulation of lipopolysaccharide-mediated response by the transmembrane adaptor protein LAB.J Immunol, vol. 188, no. 6, Mar. 2012, pp. 2733–41. Pubmed, doi:10.4049/jimmunol.1101581.
Zhu M, Fuller DM, Ou-Yang C-W, Sullivan SA, Zhang W. Tyrosine phosphorylation-independent regulation of lipopolysaccharide-mediated response by the transmembrane adaptor protein LAB. J Immunol. 2012 Mar 15;188(6):2733–2741.

Published In

J Immunol

DOI

EISSN

1550-6606

Publication Date

March 15, 2012

Volume

188

Issue

6

Start / End Page

2733 / 2741

Location

United States

Related Subject Headings

  • Tyrosine
  • Signal Transduction
  • Real-Time Polymerase Chain Reaction
  • Phosphorylation
  • Mice, Knockout
  • Mice
  • Lipopolysaccharides
  • Immunoprecipitation
  • Immunology
  • Immunity, Innate