Role for B-cell adapter for PI3K (BCAP) as a signaling adapter linking Toll-like receptors (TLRs) to serine/threonine kinases PI3K/Akt

Ty Dale Troutman, Wei Hu, Stephanie Fulenchek, Tetsuo Yamazaki, Tomohiro Kurosaki, J. Fernando Bazand, Chandrashekhar Pasare

Research output: Contribution to journalArticle

77 Citations (Scopus)

Abstract

Toll like receptors (TLRs) use Toll-IL-1 receptor (TIR) domain-containing adapters, such as myeloid differentiation primary response gene 88 (MyD88) and TIR domain-containing adapter inducing IFN-β (TRIF), to induce activation of transcription factors, including NF-κB, MAP kinases, and IFN regulatory factors. TLR signaling also leads to activation of PI3K, but the molecular mechanism is not understood. Here we have discovered a unique role for B-cell adapter for PI3K (BCAP) in the TLR-signaling pathway. We find that BCAP has a functional N-terminal TIR homology domain and links TLR signaling to activation of PI3K. In addition, BCAP negatively regulates proinflammatory cytokine secretion upon TLR stimulation. In vivo, the absence of BCAP leads to exaggerated recruitment of inflammatory myeloid cells following infections and enhanced susceptibility to dextran sulfate sodium-induced colitis. Our results demonstrate that BCAP is a unique TIR domain-containing TLR signaling adapter crucial for linking TLRs to PI3K activation and regulating the inflammatory response.

Original languageEnglish (US)
Pages (from-to)273-278
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume109
Issue number1
DOIs
StatePublished - Jan 3 2012

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Toll-Like Receptors
Protein-Serine-Threonine Kinases
Phosphatidylinositol 3-Kinases
B-Lymphocytes
Interleukin-1 Receptors
Dextran Sulfate
Myeloid Cells
Colitis
Transcription Factors
Phosphotransferases
Cytokines
Infection
Genes

Keywords

  • Inflammation
  • Innate immunity
  • Macrophage
  • Negative regulator
  • Pattern recognition receptors

ASJC Scopus subject areas

  • General

Cite this

Role for B-cell adapter for PI3K (BCAP) as a signaling adapter linking Toll-like receptors (TLRs) to serine/threonine kinases PI3K/Akt. / Troutman, Ty Dale; Hu, Wei; Fulenchek, Stephanie; Yamazaki, Tetsuo; Kurosaki, Tomohiro; Bazand, J. Fernando; Pasare, Chandrashekhar.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 109, No. 1, 03.01.2012, p. 273-278.

Research output: Contribution to journalArticle

Troutman, Ty Dale ; Hu, Wei ; Fulenchek, Stephanie ; Yamazaki, Tetsuo ; Kurosaki, Tomohiro ; Bazand, J. Fernando ; Pasare, Chandrashekhar. / Role for B-cell adapter for PI3K (BCAP) as a signaling adapter linking Toll-like receptors (TLRs) to serine/threonine kinases PI3K/Akt. In: Proceedings of the National Academy of Sciences of the United States of America. 2012 ; Vol. 109, No. 1. pp. 273-278.
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