@article{morioka_broglie_omori_ikeda_takaesu_matsumoto_ninomiya-tsuji_2014, title={TAK1 kinase switches cell fate from apoptosis to necrosis following TNF stimulation}, volume={204}, number={4}, journal={Journal of Cell Biology}, author={Morioka, S. and Broglie, P. and Omori, E. and Ikeda, Y. and Takaesu, G. and Matsumoto, K. and Ninomiya-Tsuji, J.}, year={2014}, pages={607–623} }
 @article{broglie_matsumoto_akira_brautigan_ninomiya-tsuji_2010, title={Transforming Growth Factor beta-activated Kinase 1 (TAK1) Kinase Adaptor, TAK1-binding Protein 2, Plays Dual Roles in TAK1 Signaling by Recruiting Both an Activator and an Inhibitor of TAK1 Kinase in Tumor Necrosis Factor Signaling Pathway}, volume={285}, ISSN={["1083-351X"]}, DOI={10.1074/jbc.M109.090522}, abstractNote={Transforming growth factor β-activated kinase 1 (TAK1) kinase is an indispensable signaling intermediate in tumor necrosis factor (TNF), interleukin 1, and Toll-like receptor signaling pathways. TAK1-binding protein 2 (TAB2) and its closely related protein, TAB3, are binding partners of TAK1 and have previously been identified as adaptors of TAK1 that recruit TAK1 to a TNF receptor signaling complex. TAB2 and TAB3 redundantly mediate activation of TAK1. In this study, we investigated the role of TAB2 by analyzing fibroblasts having targeted deletion of the tab2 gene. In TAB2-deficient fibroblasts, TAK1 was associated with TAB3 and was activated following TNF stimulation. However, TAB2-deficient fibroblasts displayed a significantly prolonged activation of TAK1 compared with wild type control cells. This suggests that TAB2 mediates deactivation of TAK1. We found that a TAK1-negative regulator, protein phosphatase 6 (PP6), was recruited to the TAK1 complex in wild type but not in TAB2-deficient fibroblasts. Furthermore, we demonstrated that both PP6 and TAB2 interacted with the polyubiquitin chains and this interaction mediated the assembly with TAK1. Our results indicate that TAB2 not only activates TAK1 but also plays an essential role in the deactivation of TAK1 by recruiting PP6 through a polyubiquitin chain-dependent mechanism.}, number={4}, journal={JOURNAL OF BIOLOGICAL CHEMISTRY}, author={Broglie, Peter and Matsumoto, Kunihiro and Akira, Shizuo and Brautigan, David L. and Ninomiya-Tsuji, Jun}, year={2010}, month={Jan}, pages={2333–2339} }
 @article{prickett_ninomiya-tsuji_broglie_muratore-schroeder_shabanowitz_hunt_brautigan_2008, title={TAB4 stimulates TAK1-TAB1 phosphorylation and binds polyubiquitin to direct signaling to NF-kappa B}, volume={283}, ISSN={["1083-351X"]}, DOI={10.1074/jbc.m800943200}, abstractNote={Responses to transforming growth factor β and multiple cytokines involve activation of transforming growth factor β-activated kinase-1 (TAK1) kinase, which activates kinases IκB kinase (IKK) and MKK3/6, leading to the parallel activation of NF-κB and p38 MAPK. Activation of TAK1 by autophosphorylation is known to involve three different TAK1-binding proteins (TABs). Here we report a protein phosphatase subunit known as type 2A phosphatase-interacting protein (TIP) that also acts as a TAB because it co-precipitates with and directly binds to TAK1, enhances TAK1 autophosphorylation at unique sites, and promotes TAK1 phosphorylation of IKKβ and signaling to NF-κB. Mass spectrometry demonstrated that co-expression of TAB4 protein significantly increased phosphorylation of four sites in TAK1, in a linker region between the kinase and TAB2/3 binding domains, and two sites in TAB1. Recombinant GST-TAB4 bound in an overlay assay directly to inactive TAK1 and activated TAK1 but not TAK1 phosphorylated in the linker sites, suggesting a bind and release mechanism. In kinase assays using TAK1 immune complexes, added GST-TAB4 selectively stimulated IKK phosphorylation. TAB4 co-precipitated polyubiquitinated proteins dependent on a Phe-Pro motif that was required to enhance phosphorylation of TAK1. TAB4 mutated at Phe-Pro dominantly interfered with IL-1β activation of NF-κB involving IKK-dependent but not p38 MAPK-dependent signaling. The results show that TAB4 binds TAK1 and polyubiquitin chains to promote specific sites of phosphorylation in TAK1-TAB1, which activates IKK signaling to NF-κB.}, number={28}, journal={JOURNAL OF BIOLOGICAL CHEMISTRY}, author={Prickett, Todd D. and Ninomiya-Tsuji, Jun and Broglie, Peter and Muratore-Schroeder, Tara L. and Shabanowitz, Jeffrey and Hunt, Donald F. and Brautigan, David L.}, year={2008}, month={Jul}, pages={19245–19254} }