Back to Search
Start Over
TAB1 modulates IL-1α mediated cytokine secretion but is dispensable for TAK1 activation
- Source :
- Cellular Signalling. 19:646-657
- Publication Year :
- 2007
- Publisher :
- Elsevier BV, 2007.
-
Abstract
- Biochemical evidence indicates that TGF-beta-activated kinase 1 (TAK1), a key modulator of the inflammatory response, exists in a complex with various adaptor proteins including the TAK1 binding protein 1 (TAB1). However, the physiological importance of TAB1 in TAK1 activation, and in the subsequent induction of proinflammatory mediators, remains unclear. In this study, a critical role for TAK1 in IL-1alpha or TNFalpha stimulated MAPK and NFkappaB activation was confirmed by inhibition of the nuclear accumulation of NFkappaB p65 and phosphorylated forms of c-Jun and p38 following siRNA mediated TAK1 silencing. These effects were associated with significant reductions in IL-1alpha stimulated levels of secreted IL-6, IL-8, MCP-1 and GM-CSF. In contrast, IL-1alpha or TNFalpha dependent cellular redistribution of NFkappaB p65 and phosphorylated c-Jun and p38 was not affected by 80% siRNA mediated knockdown of TAB1 protein levels. Interestingly, IL-6, IL-8 and GM-CSF release from TAB1 siRNA transfected cells was significantly reduced following IL-1alpha treatment, but was unchanged after TNFalpha stimulation, suggesting differential roles for TAB1 in IL-1alpha and TNFalpha signalling pathways. These findings may imply an as yet unidentified role for TAB1 in the inflammatory response, which is independent of the activation of classical TAK1 associated signalling cascades.
- Subjects :
- MAPK/ERK pathway
MAP kinase kinase kinase
Kinase
p38 mitogen-activated protein kinases
Signal transducing adaptor protein
Cell Biology
Biology
MAP Kinase Kinase Kinases
Proinflammatory cytokine
Cell biology
Enzyme Activation
Interleukin-1alpha
Cytokines
Humans
Cytokine secretion
Tumor necrosis factor alpha
RNA, Small Interfering
Adaptor Proteins, Signal Transducing
HeLa Cells
Subjects
Details
- ISSN :
- 08986568
- Volume :
- 19
- Database :
- OpenAIRE
- Journal :
- Cellular Signalling
- Accession number :
- edsair.doi.dedup.....1b9918d2a41dae807ad21c1712d9fe99
- Full Text :
- https://doi.org/10.1016/j.cellsig.2006.08.017