TY - JOUR
T1 - Diverse Toll-like receptors utilize Tpl2 to activate extracellular signal-regulated kinase (ERK) in hemopoietic cells
AU - Banerjee, Ashish
AU - Gugasyan, Raffi
AU - McMahon, Martin
AU - Gerondakis, Steve
PY - 2006/2/28
Y1 - 2006/2/28
N2 - 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.
AB - 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.
KW - Mitogen-activated protein kinase
KW - Rel/NF-κB
UR - http://www.scopus.com/inward/record.url?scp=33644761875&partnerID=8YFLogxK
U2 - 10.1073/pnas.0511113103
DO - 10.1073/pnas.0511113103
M3 - Article
C2 - 16484370
AN - SCOPUS:33644761875
SN - 0027-8424
VL - 103
SP - 3274
EP - 3279
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 9
ER -