Diverse Toll-like receptors utilize Tpl2 to activate extracellular signal-regulated kinase (ERK) in hemopoietic cells

Ashish Banerjee, Raffi Gugasyan, Martin McMahon, Steve Gerondakis

Research output: Contribution to journalArticleResearchpeer-review

131 Citations (Scopus)

Abstract

Engaging mammalian Toll-like receptors (TLRs) activate both the NF-κB and mitogen-activated protein kinase signaling pathways. Here we establish that mitogen-activated protein 3 kinase Tpl2, levels of which are markedly reduced in nfkb1-/- cells, is required for extracellular signal-regulated kinase (ERK) activation in bone marrow-derived macrophages and B cells stimulated with diverse TLR ligands. Despite rescuing TLR-dependent ERK activation in nfkb1-/- bone marrow-derived macrophages by using an estrogen receptor-regulated version of the mitogen-activated protein 3 kinase, c-Raf (Raf:ER), CpG or LPS induction of IL-10 was only partially restored in nfkb1-/- cells expressing Raf:ER, a finding consistent with NF-κB1 regulating IL-10 by a combination of ERK-independent and -dependent mechanisms. Collectively, our findings indicate that the Tpl2/MEK/ERK signaling module is a master regulator of ERK-dependent gene expression downstream of TLRs in different hemopoietic cells.

Original languageEnglish
Pages (from-to)3274-3279
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume103
Issue number9
DOIs
Publication statusPublished - 28 Feb 2006
Externally publishedYes

Keywords

  • Mitogen-activated protein kinase
  • Rel/NF-κB

Cite this