TAB1 modulates IL-1α mediated cytokine secretion but is dispensable for TAK1 activation
- 作者：Malene Bertelsen ; Annika Sanfridson
- 关键词：TAB1 ; TAK1 ; Translocation ; MAPK ; NFκ ; B ; Cytokines
- 刊名：Cellular Signalling
- 出版年：2007
- 期刊代码：42_08986568
- 类别：bio
- 出版时间：March 2007
- 卷：19
- 期：3
- 页码：646-657
- 文件大小：1255 K
摘要
Biochemical evidence indicates that TGF-β-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-1α or TNFα stimulated MAPK and NFκB activation was confirmed by inhibition of the nuclear accumulation of NFκB p65 and phosphorylated forms of c-Jun and p38 following siRNA mediated TAK1 silencing. These effects were associated with significant reductions in IL-1α stimulated levels of secreted IL-6, IL-8, MCP-1 and GM-CSF. In contrast, IL-1α or TNFα dependent cellular redistribution of NFκB 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-1α treatment, but was unchanged after TNFα stimulation, suggesting differential roles for TAB1 in IL-1α and TNFα 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.