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PMID:21602844
| Citation |
Seit-Nebi, A, Cheng, W, Xu, H and Han, J (2012) MLK4 has negative effect on TLR4 signaling. Cell. Mol. Immunol. 9:27-33 |
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| Abstract |
The stimulation of Toll-like receptors (TLRs) on macrophages triggers production of proinflammatory cytokines such as tumor-necrosis factor-α (TNF-α). The TNF production is mediated by a series of signaling events and subsequent transcriptional and post-transcriptional activation of the TNF gene. Termination of TLR-mediated cellular signaling is also important for a proper immunoresponse, since sustained cytokine expression can result in immune disorders. Here we identified that mixed-lineage kinase (MLK) 4 is a TLR4-interacting protein. Unlike previously characterized MLK group members, MLK4 cannot act as a mitogen-activated protein kinase kinase kinase (MAP3K) to mediate c-Jun N-terminal kinase (JNK), p38 or extracellular signal-regulated kinase (ERK) activation. Rather, MLK4 appears to be able to inhibit lipopolysaccharide (LPS)-induced activation of the JNK or ERK pathways, but does not have effect on LPS-induced p38 or NF-κB activation. The LPS-induced TNF production in MLK4 knockdown and overexpression cells were also increased and reduced, respectively. These data demonstrate that MLK4 is a negative regulator of TLR4 signaling. |
| Links |
PubMed PMC3161176 Online version:10.1038/cmi.2011.15 |
| Keywords |
Animals; Enzyme Activation/drug effects; Enzyme Activation/genetics; Enzyme Activation/immunology; Gene Knockdown Techniques; HEK293 Cells; Humans; Lipopolysaccharides/pharmacology; MAP Kinase Kinase 4/genetics; MAP Kinase Kinase 4/immunology; MAP Kinase Kinase Kinases/genetics; MAP Kinase Kinase Kinases/immunology; MAP Kinase Signaling System/drug effects; MAP Kinase Signaling System/immunology; Mice; Toll-Like Receptor 4/genetics; Toll-Like Receptor 4/immunology; p38 Mitogen-Activated Protein Kinases/genetics; p38 Mitogen-Activated Protein Kinases/immunology |
| edit table |
Significance
Annotations
| Gene product | Qualifier | GO Term | Evidence Code | with/from | Aspect | Extension | Notes | Status |
|---|---|---|---|---|---|---|---|---|
|
Colocalizes with |
GO:0031665: negative regulation of lipopolysaccharide-mediated signaling pathway |
ECO:0000314: |
P |
Looking at Figure 5 it proves that this protein negatively regulates LSP |
complete | |||
See also
References
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