@article{hsieh_agarwal_cholok_loder_kaneko_huber_chung_ranganathan_habbouche_li_et al._2019, title={Coordinating Tissue Regeneration Through Transforming Growth Factor-beta Activated Kinase 1 Inactivation and Reactivation}, volume={37}, ISSN={["1549-4918"]}, DOI={10.1002/stem.2991}, abstractNote={Abstract}, number={6}, journal={STEM CELLS}, author={Hsieh, Hsiao Hsin Sung and Agarwal, Shailesh and Cholok, David J. and Loder, Shawn J. and Kaneko, Kieko and Huber, Amanda and Chung, Michael T. and Ranganathan, Kavitha and Habbouche, Joe and Li, John and et al.}, year={2019}, month={Jun}, pages={766–778} }
 @article{lane_yumoto_azhar_ninomiya-tsuji_inagaki_hu_deng_kim_mishina_kaartinen_2015, title={Tak1, Smad4 and Trim33 redundantly mediate TGF-beta 3 signaling during palate development}, volume={398}, ISSN={["1095-564X"]}, DOI={10.1016/j.ydbio.2014.12.006}, abstractNote={Transforming growth factor-beta3 (TGF-β3) plays a critical role in palatal epithelial cells by inducing palatal epithelial fusion, failure of which results in cleft palate, one of the most common birth defects in humans. Recent studies have shown that Smad-dependent and Smad-independent pathways work redundantly to transduce TGF-β3 signaling in palatal epithelial cells. However, detailed mechanisms by which this signaling is mediated still remain to be elucidated. Here we show that TGF-β activated kinase-1 (Tak1) and Smad4 interact genetically in palatal epithelial fusion. While simultaneous abrogation of both Tak1 and Smad4 in palatal epithelial cells resulted in characteristic defects in the anterior and posterior secondary palate, these phenotypes were less severe than those seen in the corresponding Tgfb3 mutants. Moreover, our results demonstrate that Trim33, a novel chromatin reader and regulator of TGF-β signaling, cooperates with Smad4 during palatogenesis. Unlike the epithelium-specific Smad4 mutants, epithelium-specific Tak1:Smad4- and Trim33:Smad4-double mutants display reduced expression of Mmp13 in palatal medial edge epithelial cells, suggesting that both of these redundant mechanisms are required for appropriate TGF-β signal transduction. Moreover, we show that inactivation of Tak1 in Trim33:Smad4 double conditional knockouts leads to the palatal phenotypes which are identical to those seen in epithelium-specific Tgfb3 mutants. To conclude, our data reveal added complexity in TGF-β signaling during palatogenesis and demonstrate that functionally redundant pathways involving Smad4, Tak1 and Trim33 regulate palatal epithelial fusion.}, number={2}, journal={DEVELOPMENTAL BIOLOGY}, author={Lane, Jamie and Yumoto, Kenji and Azhar, Mohamad and Ninomiya-Tsuji, Jun and Inagaki, Maiko and Hu, Yingling and Deng, Chu-Xia and Kim, Jieun and Mishina, Yuji and Kaartinen, Vesa}, year={2015}, month={Feb}, pages={231–241} }
 @article{yumoto_thomas_lane_matsuzaki_inagaki_ninomiya-tsuji_scott_ray_ishii_maxson_et al._2013, title={TGF-beta-activated Kinase 1 (Tak1) Mediates Agonist-induced Smad Activation and Linker Region Phosphorylation in Embryonic Craniofacial Neural Crest-derived Cells}, volume={288}, ISSN={["1083-351X"]}, DOI={10.1074/jbc.m112.431775}, abstractNote={Background: The role of Smad-independent TGF-β signaling in craniofacial development is poorly elucidated. Results: In craniofacial mesenchymal cells, Tak1 regulates both R-Smad C-terminal and linker region phosphorylation in TGF-β signaling. Conclusion: Tak1 plays an irreplaceable role in craniofacial ecto-mesenchyme during embryogenesis. Significance: Understanding the mechanisms of TGF-β signaling contributes to knowledge of pathogenetic mechanisms underlying common craniofacial birth defects. Although the importance of TGF-β superfamily signaling in craniofacial growth and patterning is well established, the precise details of its signaling mechanisms are still poorly understood. This is in part because of the concentration of studies on the role of the Smad-dependent (so-called “canonical”) signaling pathways relative to the Smad-independent ones in many biological processes. Here, we have addressed the role of TGF-β-activated kinase 1 (Tak1, Map3k7), one of the key mediators of Smad-independent (noncanonical) TGF-β superfamily signaling in craniofacial development, by deleting Tak1 specifically in the neural crest lineage. Tak1-deficient mutants display a round skull, hypoplastic maxilla and mandible, and cleft palate resulting from a failure of palatal shelves to appropriately elevate and fuse. Our studies show that in neural crest-derived craniofacial ecto-mesenchymal cells, Tak1 is not only required for TGF-β- and bone morphogenetic protein-induced p38 Mapk activation but also plays a role in agonist-induced C-terminal and linker region phosphorylation of the receptor-mediated R-Smads. Specifically, we demonstrate that the agonist-induced linker region phosphorylation of Smad2 at Thr-220, which has been shown to be critical for full transcriptional activity of Smad2, is dependent on Tak1 activity and that in palatal mesenchymal cells TGFβRI and Tak1 kinases mediate both overlapping and distinct TGF-β2-induced transcriptional responses. To summarize, our results suggest that in neural crest-derived ecto-mesenchymal cells, Tak1 provides a critical point of intersection in a complex dialogue between the canonical and noncanonical arms of TGF-β superfamily signaling required for normal craniofacial development.}, number={19}, journal={JOURNAL OF BIOLOGICAL CHEMISTRY}, author={Yumoto, Kenji and Thomas, Penny S. and Lane, Jamie and Matsuzaki, Kouichi and Inagaki, Maiko and Ninomiya-Tsuji, Jun and Scott, Gregory J. and Ray, Manas K. and Ishii, Mamoru and Maxson, Robert and et al.}, year={2013}, month={May}, pages={13467–13480} }
 @article{takaesu_inagaki_takubo_mishina_hess_dean_yoshimura_matsumoto_suda_ninomiya-tsuji_et al._2012, title={TAK1 (MAP3K7) Signaling Regulates Hematopoietic Stem Cells through TNF-Dependent and -Independent Mechanisms}, volume={7}, ISSN={1932-6203}, url={http://dx.doi.org/10.1371/journal.pone.0051073}, DOI={10.1371/journal.pone.0051073}, abstractNote={A cytokine/stress signaling kinase Tak1 (Map3k7) deficiency is known to impair hematopoietic progenitor cells. However, the role of TAK1 signaling in the stem cell function of the hematopoietic system is not yet well defined. Here we characterized hematopoietic stem cells (HSCs) harboring deletion of Tak1 and its activators, Tak1 binding proteins 1 and 2 (Tab1 and Tab2) using a competitive transplantation assay in a mouse model. Tak1 single or Tab1/Tab2 double deletions completely eliminated the reconstitution activity of HSCs, whereas Tab1 or Tab2 single deletion did not cause any abnormality. Tak1 single or Tab1/Tab2 double deficient lineage-negative, Sca-1+, c-Kit+ (LSK) cells did not proliferate and underwent cell death. We found that Tnfr1 deficiency restored the reconstitution activity of Tak1 deficient bone marrow cells for 6–18 weeks. However, the reconstitution activity of Tak1- and Tnfr1-double deficient bone marrow cells declined over the long term, and the number of phenotypically identified long-term hematopoietic stem cells were diminished. Our results indicate that TAB1- or TAB2-dependent activation of TAK1 is required for maintenance of the hematopoietic system through two mechanisms: one is prevention of TNF-dependent cell death and the other is TNF-independent maintenance of long-term HSC.}, number={11}, journal={PLoS ONE}, publisher={Public Library of Science (PLoS)}, author={Takaesu, Giichi and Inagaki, Maiko and Takubo, Keiyo and Mishina, Yuji and Hess, Paul R. and Dean, Gregg A. and Yoshimura, Akihiko and Matsumoto, Kunihiro and Suda, Toshio and Ninomiya-Tsuji, Jun and et al.}, editor={Tjwa, MarcEditor}, year={2012}, month={Nov}, pages={e51073} }
 @article{inagaki_komatsu_scott_yamada_ray_ninomiya-tsuji_mishina_2008, title={Generation of a conditional mutant allele for Tab1 in mouse}, volume={46}, ISSN={["1526-968X"]}, DOI={10.1002/dvg.20418}, abstractNote={Abstract}, number={8}, journal={GENESIS}, author={Inagaki, Maiko and Komatsu, Yoshihiro and Scott, Greg and Yamada, Gen and Ray, Manas and Ninomiya-Tsuji, Jun and Mishina, Yuji}, year={2008}, month={Aug}, pages={431–439} }
 @article{inagaki_omori_kim_komatsu_scott_ray_yamada_matsumoto_mishina_ninomiya-tsuji_2008, title={TAK1-binding Protein 1, TAB1, Mediates Osmotic Stress-induced TAK1 Activation but Is Dispensable for TAK1-mediated Cytokine Signaling}, volume={283}, ISSN={["1083-351X"]}, DOI={10.1074/jbc.M807574200}, abstractNote={TAK1 kinase is an indispensable intermediate in several cytokine signaling pathways including tumor necrosis factor, interleukin-1, and transforming growth factor-β signaling pathways. TAK1 also participates in stress-activated intracellular signaling pathways such as osmotic stress signaling pathway. TAK1-binding protein 1 (TAB1) is constitutively associated with TAK1 through its C-terminal region. Although TAB1 is known to augment TAK1 catalytic activity when it is overexpressed, the role of TAB1 under physiological conditions has not yet been identified. In this study, we determined the role of TAB1 in TAK1 signaling by analyzing TAB1-deficient mouse embryonic fibroblasts (MEFs). Tumor necrosis factor- and interleukin-1-induced activation of TAK1 was entirely normal in Tab1-deficient MEFs and could activate both mitogen-activated protein kinases and NF-κB. In contrast, we found that osmotic stress-induced activation of TAK1 was largely impaired in Tab1-deficient MEFs. Furthermore, we showed that the C-terminal 68 amino acids of TAB1 were sufficient to mediate osmotic stress-induced TAK1 activation. Finally, we attempted to determine the mechanism by which TAB1 activates TAK1. We found that TAK1 is spontaneously activated when the concentration is increased and that it is totally dependent on TAB1. Cell shrinkage under the osmotic stress condition increases the concentration of TAB1-TAK1 and may oligomerize and activate TAK1 in a TAB1-dependent manner. These results demonstrate that TAB1 mediates TAK1 activation only in a subset of TAK1 pathways that are mediated through spontaneous oligomerization of TAB1-TAK1.}, number={48}, journal={JOURNAL OF BIOLOGICAL CHEMISTRY}, author={Inagaki, Maiko and Omori, Emily and Kim, Jae-Young and Komatsu, Yoshihiro and Scott, Greg and Ray, Manas K. and Yamada, Gen and Matsumoto, Kunihiro and Mishina, Yuji and Ninomiya-Tsuji, Jun}, year={2008}, month={Nov}, pages={33080–33086} }