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Hokkaido University Collection of Scholarly and Academic Papers >
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Apoptosis signal-regulating kinase 1-mediated sustained p38 mitogen-activated protein kinase activation regulates mycoplasmal lipoprotein- and staphylococcal peptidoglycan-triggered Toll-like receptor 2 signalling pathways
| Title: | Apoptosis signal-regulating kinase 1-mediated sustained p38 mitogen-activated protein kinase activation regulates mycoplasmal lipoprotein- and staphylococcal peptidoglycan-triggered Toll-like receptor 2 signalling pathways |
| Authors: | Into, Takeshi Browse this author | | Shibata, Ken-ichiro Browse this author |
| Keywords: | TLR2 | | ASK1 | | p38 MAPK | | AP-1 | | NF-κB | | caspase |
| Issue Date: | Sep-2005 |
| Publisher: | Blackwell Publishing |
| Journal Title: | Cellular Microbiology |
| Volume: | 7 |
| Issue: | 9 |
| Start Page: | 1305 |
| End Page: | 1317 |
| Publisher DOI: | 10.1111/j.1462-5822.2005.00558.x |
| PMID: | 16098218 |
| Abstract: | Toll-like receptor (TLR) 2 functions as a sensor for detecting various microbial components conserved in bacteria or fungi in innate immunity. TLR2 induces several signalling pathways linking to activation of the transcriptional factors NF-κB and AP-1 as well as induction of cell death. In human embryonic kidney 293 cells expressed human TLR2, mycoplasmal lipoproteins (MLP) or staphylococcal peptidoglycans (PGN) induced sustained phosphorylation of p38 mitogen-activated protein kinase (MAPK), accompanied by generation of reactive oxygen species. This observation encouraged us to examine roles of apoptosis signal-regulating kinase 1 (ASK1) in TLR2 signalling, because ASK1 is an upstream activator of p38 MAPK during exposure to oxidative stress and other stressful stimuli. A kinase-inactive mutant of ASK1 greatly impaired the sustained phosphorylation of p38 MAPK induced by MLP or PGN. This mutant also attenuated MLP- or PGN-induced transcriptional activities of NF-κB and AP-1 via inhibition of p38 MAPK activation. MLP- or PGN-induced cell death reactions, including DNA fragmentation and caspase-3/7 activation, were also downregulated by the ASK1 mutant via p38 MAPK inhibition. Furthermore, TLR2 signalling had a potential to phosphorylate and dephosphorylate ASK1 at Ser83 residue. Thus, MLP and PGN have capabilities to induce ASK1-dependent signalling pathways which regulate p38 MAPK activation through TLR2, leading to activation of NF-κB and AP-1 as well as induction of cell death. |
| Rights: | The definitive version is available at www.blackwell-synergy.com |
| Type: | article (author version) |
| URI: | http://hdl.handle.net/2115/30270 |
| Appears in Collections: | 歯学院・歯学研究院 (Graduate School of Dental Medicine / Faculty of Dental Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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Submitter: 柴田 健一郎
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