Diverse Toll-like receptors utilize Tpl2 to activate extracellular signal-regulated kinase (ERK) in hemopoietic cells
- Author(s)
- Banerjee, A; Gugasyan, R; McMahon, M; Gerondakis, S;
- Details
- Publication Year 2006-02-28,Volume 103,Issue #9,Page 3274-3279
- Journal Title
- PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
- Publication Type
- Journal Article
- Abstract
- Engaging mammalian Toll-like receptors (TLRs) activate both the NF-kappa B 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-kappa B1 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.
- Publisher
- NATL ACAD SCIENCES
- Keywords
- KAPPA-B; PROTEIN-KINASE; DENDRITIC CELLS; ADAPTER MOLECULE; IL-12 PRODUCTION; NUCLEAR-FACTOR; CPG DNA; C-FOS; EXPRESSION; INDUCTION
- Publisher's Version
- https://doi.org/10.1073/pnas.0511113103
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2006-02-28 12:00:00