TAB2, a Novel Adaptor Protein, Mediates Activation of TAK1 MAPKKK by Linking TAK1 to TRAF6 in the IL-1 Signal Transduction Pathway

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Interleukin-1 and TRAF6-dependent activation of TAK1 in the absence of TAB2 and TAB3

Interleukin-1 (IL-1) signaling induces the formation of Lys63-linked ubiquitin (K63-Ub) chains, which are thought to activate the 'master' protein kinase TGFβ-activated kinase 1 (TAK1) by interacting with its TAK1-binding 2 (TAB2) and TAB3 subunits. Here, we report that IL-1β can also activate the TAB1-TAK1 heterodimer present in TAB2/TAB3 double knockout (DKO) IL-1 receptor-expressing cells. T...

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Interleukin-1 (IL-1) receptor-associated kinase-dependent IL-1-induced signaling complexes phosphorylate TAK1 and TAB2 at the plasma membrane and activate TAK1 in the cytosol.

Interleukin-1 (IL-1) receptor-associated kinase (IRAK) plays an important role in the sequential formation and activation of IL-1-induced signaling complexes. Previous studies showed that IRAK is recruited to the IL-1-receptor complex, where it is hyperphosphorylated. We now find that the phosphorylated IRAK in turn recruits TRAF6 to the receptor complex (complex I), which differs from the prev...

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TAK1-dependent signaling requires functional interaction with TAB2/TAB3.

Transforming growth factor beta-activated kinase 1 (TAK1), a member of the MAPKKK family, was initially described to play an essential role in the transforming growth factor beta-signaling pathway, but recent evidence has emerged implicating TAK1 in the interleukin (IL)-1 and tumor necrosis factor (TNF) pathways. Notably, two homologous proteins, TAB2 and TAB3, have been identified as adaptors ...

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TRAF6 Autoubiquitination-Independent Activation of the NFκB and MAPK Pathways in Response to IL-1 and RANKL

The adapter protein TRAF6 is critical for mediating signal transduction from members of the IL-1R/TLR and TNFR superfamilies. The TRAF6 RING finger domain functions as an ubiquitin E3 ligase capable of generating non-degradative K63-linked ubiquitin chains. It is believed that these chains serve as docking sites for formation of signaling complexes, and that K63-linked autoubiquitination of TRA...

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Transforming growth factor-β (TGF-β) principally relays its effects through the Smad pathway however, accumulating evidence indicate that alternative signaling routes are also employed by this pleiotropic cytokine. For instance recently, we have demonstrated that ligand occupied TGF-β receptors can directly trigger the TRAF6-TAK1 signaling module, resulting in MAP kinase activation. Here we rep...

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ژورنال

عنوان ژورنال: Molecular Cell

سال: 2000

ISSN: 1097-2765

DOI: 10.1016/s1097-2765(00)80244-0