<scp>TAK</scp>1 adaptor proteins, <scp>TAB</scp>2 and <scp>TAB</scp>3, link the signalosome to B‐cell receptor‐induced <scp>IKK</scp> activation

Shinohara, Hisaaki; Yasuda, Tomoharu; Kurosaki, Tomohiro

doi:10.1002/1873-3468.12342

Cited by 5 publications

(7 citation statements)

References 23 publications

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“…Together with the role TAK1 plays in the MAPK pathway, it is also well documented as important in mediating NF‐κB activity in various cell types including HeLa, HEK293T, ex vivo neurons, microglia cells, and B and T lymphocytes, to name a few 24 , 45 48–52 ; however, the precise nature of the TAK1 role has been a challenge to dissect at times. In B cell receptor (BCR) signaling, based on differential knockout models, the kinase activity of TAK1 was shown to be dispensable on the one hand, 45 while others later demonstrated that the physical protein, likely via its interactions 53 (e.g., TAB2 and TAB3) were critical 52 . Evidence to support the conservation of this role in the context of allergen‐challenged mast cells has not been documented.…”

Section: Discussionmentioning

confidence: 99%

“…In B cell receptor (BCR) signaling, based on differential knockout models, the kinase activity of TAK1 was shown to be dispensable on the one hand, 45 while others later demonstrated that the physical protein, likely via its interactions 53 (e.g., TAB2 and TAB3) were critical. 52 Evidence to support the conservation of this role in the context of allergen-challenged mast cells has not been documented. Here, we sought to determine whether TAK1 activity-dependent NF-B signaling function would be conserved in mast cells, as a molecule with dual MAPK and NF-B regulatory function might carry substantial impact on the production of mast cell inflammatory mediators.…”

Section: Discussionmentioning

confidence: 99%

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TAK1 signaling activity links the mast cell cytokine response and degranulation in allergic inflammation

Watson

Maguire

Rouillard

et al. 2020

Journal of Leukocyte Biology

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Mast cells drive the inappropriate immune response characteristic of allergic inflammatory disorders via release of pro‐inflammatory mediators in response to environmental cues detected by the IgE‐FcεRI complex. The role of TGF‐β‐activated kinase 1 (TAK1), a participant in related signaling in other contexts, remains unknown in allergy. We detect novel activation of TAK1 at Ser412 in response to IgE‐mediated activation under SCF‐c‐kit potentiation in a mast cell‐driven response characteristic of allergic inflammation, which is potently blocked by TAK1 inhibitor 5Z‐7‐oxozeaenol (OZ). We, therefore, interrogated the role of TAK1 in a series of mast cell‐mediated responses using IgE‐sensitized murine bone marrow‐derived mast cells, stimulated with allergen under several TAK1 inhibition strategies. TAK1 inhibition by OZ resulted in significant impairment in the phosphorylation of MAPKs p38, ERK, and JNK; and mediation of the NF‐κB pathway via IκBα. Impaired gene expression and near abrogation in release of pro‐inflammatory cytokines TNF, IL‐6, IL‐13, and chemokines CCL1, and CCL2 was detected. Finally, a significant inhibition of mast cell degranulation, accompanied by an impairment in calcium mobilization, was observed in TAK1‐inhibited cells. These results suggest that TAK1 acts as a signaling node, not only linking the MAPK and NF‐κB pathways in driving the late‐phase response, but also initiation of the degranulation mechanism of the mast cell early‐phase response following allergen recognition and may warrant consideration in future therapeutic development.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

TAK1 signaling activity links the mast cell cytokine response and degranulation in allergic inflammation

Watson

Maguire

Rouillard

et al. 2020

Journal of Leukocyte Biology

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“…data]. TAB3 is an adaptor molecule that, in combination with protein kinase TAK1, phosphorylates the subunit of NFκB, IκBα/β and leads to NFκB activation [23, 24]. Data on the potential role of TAB3 in the context of allergy is limited.…”

Section: Discussionmentioning

confidence: 99%

“…A possible explanation may be that patients with allergies have a lower constitutive TAB3 expression reflecting their atopic status. Studies described in cancer research showed TAB3 as one of the important molecules in a cascade of genes forming the NFκB activation pathway [24, 26]. …”

Section: Discussionmentioning

confidence: 99%

Evidence for a Role of TGF-β-Activated Kinase 1 and MAP3K7 Binding Protein 3 in Peanut-Specific T-Cell Responses

Saidova

Bublin

Schmidthaler

et al. 2019

Int Arch Allergy Immunol

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Peanut allergy is considered to be the most common cause for food-induced anaphylaxis. Currently, no approved treatment is available. Avoidance is the only measure to prevent anaphylactic reactions to peanuts. T-helper cells are of special importance for the sensitization process and the maintenance of allergic inflammation. Identifying markers of allergen-specific T-cell responses may help to develop novel treatment approaches. Therefore, we aimed to define new T-cell target genes in Ara h 2-specific T cells and to investigate the possibility of using them as biomarkers of peanut allergy in peripheral blood mononuclear cells (PBMCs). We performed whole mRNA array analysis (whole human genome oligo microarray) of in vitro expanded Ara h 2-specific T cells (CFSE^lowCD3⁺CD4⁺) from 5 peanut-allergic (PA) and 5 non-peanut-sensitized individuals. Expression of selected genes as a result of a two-step bioinformatic approach was confirmed in a second cohort by quantitative PCR. TGF-β- activated kinase 1 and MAP3K7 binding protein 3 (TAB3), calcium/calmodulin-dependent protein kinase type IV (CAMK4) and HemK methyltransferase family member 1 (HEMK1) were significantly upregulated in Ara h 2-specific T cells of PA patients. In addition, the expression of these genes was also assessed in unstimulated PBMCs from a cohort (n = 43) of PA, atopic non-PA, and nonatopic controls. Interestingly, in unstimulated PBMCs, TAB3 expression was significantly downregulated in PA patients compared to atopic non-PA individuals. Thus, TAB3 may play a significant role at the level of T-cell activation and may also be a candidate biomarker for PA.

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“…Recently, several studies revealed the biological functions of TAB3 in different cells (Mendoza et al, 2008;Min et al, 2012;Hu et al, 2015;Shinohara et al, 2016). Of these properties, apoptosis induction and proliferation inhibition by TAB3 have garnered attention from researchers.…”

Section: Discussionmentioning

confidence: 99%

TAB3 defect induces augmented cardioprotection loss from ischemic injury

Sheng

Zeng

2017

Cell Biology International

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The transforming growth factor β-activated kinase-binding protein 3 (TAB3) plays a crucial role in modulating cell apoptosis and proliferation in many diseases, including hepatocellular carcinoma, lung cancer, and intracerebral hemorrhage. However, the functional role of TAB3 in the heart is not well reported. In our study, we first investigated the role of TAB3 in ischemia heart diseases. For in vitro studies, cardiomyocytes (CMs) were isolated from both TAB3 knockout (KO) and wild-type (WT) mice, and the apoptosis ratios were tested after a 48-h ischemic stimulation. A proliferation test and tubeformation assay were underwent at normoxia condition. For in vivo studies, the MI model was completed for both TAB3 KO and WT mice. Echocardiography was evaluated at 3 days and 28 days post-MI, whereas the hemodynamics test was performed 28 days post-MI. The histology results of the apoptosis, proliferation of myocardium, neovasculation of microvessels, and infarct zone assessments were determined using terminal deoxynucleotidyl transferase dUTP nick end labeling staining, Ki67 immunostaining, α-SMA/CD31 immunostaining, and the Masson-Trichrome method, respectively. Expression changes of the related proteins caused by TAB3 deficiency were confirmed using both quantitative real-time polymerase chain reaction and immunoblotting. Our results indicate that the absence of TAB3 induced more CMs apoptosis, decrease cardiomyocyte proliferation, and weaker angiogenesis in vitro and in vivo. Worse cardiac function and enlarged scar formation were detected in TAB3 KO mice, and increased expression of active-caspase-3 and decreased expression of NF-κB/p65, Akt, Bcl-2/Bax, and VEGF occurred. In summary, our findings indicate that the absence of TAB3 plays a harmful role in ischemic heart disease.

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TAK1 adaptor proteins, TAB2 and TAB3, link the signalosome to B‐cell receptor‐induced IKK activation

Cited by 5 publications

References 23 publications

TAK1 signaling activity links the mast cell cytokine response and degranulation in allergic inflammation

TAK1 signaling activity links the mast cell cytokine response and degranulation in allergic inflammation

Evidence for a Role of TGF-β-Activated Kinase 1 and MAP3K7 Binding Protein 3 in Peanut-Specific T-Cell Responses

TAB3 defect induces augmented cardioprotection loss from ischemic injury

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