TAK1–TAB1 fusion protein: a novel constitutively active mitogen-activated protein kinase kinase kinase that stimulates AP-1 and NF-κB signaling pathways

Sakurai, Hiroaki; Nishi, Akito; Sato, Naoya; Mizukami, Junko; Miyoshi, Hidetaka; Sugita, Takahisa

doi:10.1016/s0006-291x(02)02379-3

Cited by 78 publications

(74 citation statements)

References 24 publications

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“…There have been reported two possible activating phosphorylation sites of TAK1 (42,45). We confirmed previous observations that mutations of Thr-187 or Ser-192 with Ala inhibited TAK1 kinase activity and Thr-187 phosphorylation ( Fig.…”

Section: Discussionsupporting

confidence: 92%

“…Expression Vectors-Expression vectors for TAK1, TAB1, and IKK␤ were reported previously (18,19,41,42). Point mutations were made by using a QuikChange site-directed mutagenesis kit (Stratagene), and all of the mutations were verified by DNA sequencing analysis.…”

Section: Methodsmentioning

confidence: 99%

“…TAK1 has been suggested to be phosphorylated in the stress signaling pathway. Mutational experiments defined Thr-187 and Ser-192 in the activation loop as target residues to trigger TAK1 kinase activity (41,42,45). However, there is no evidence of the phosphorylation of endogenous TAK1 under physiological conditions.…”

mentioning

confidence: 99%

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Critical Roles of Threonine 187 Phosphorylation in Cellular Stress-induced Rapid and Transient Activation of Transforming Growth Factor-β-activated Kinase 1 (TAK1) in a Signaling Complex Containing TAK1-binding Protein TAB1 and TAB2

Singhirunnusorn

Suzuki

Kawasaki

et al. 2005

Journal of Biological Chemistry

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194

189

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Section: Discussionsupporting

confidence: 92%

Section: Methodsmentioning

confidence: 99%

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Critical Roles of Threonine 187 Phosphorylation in Cellular Stress-induced Rapid and Transient Activation of Transforming Growth Factor-β-activated Kinase 1 (TAK1) in a Signaling Complex Containing TAK1-binding Protein TAB1 and TAB2

Singhirunnusorn

Suzuki

Kawasaki

et al. 2005

Journal of Biological Chemistry

Self Cite

194

189

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“…Among these activator proteins, TAB1 has been recognized to be sufficient for the association with and the induction of the catalytic activity of TAK1 (25) and also prevention of its dephosphorylation and inactivation (26). Therefore, we next investigated whether minocycline affects the interaction of TAK1 with its activator protein TAB1.…”

Section: Minocycline Suppresses Tgf-b-activated Kinase 1 Activation Amentioning

confidence: 99%

RETRACTED: Minocycline Targets the NF-κB Nexus through Suppression of TGF-β1-TAK1-IκB Signaling in Ovarian Cancer

Ataie-Kachoie

Badar

Morris

et al. 2013

Molecular Cancer Research

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Substantial evidence supports the critical role of NF-kB in ovarian cancer. Minocycline, a tetracycline, has been shown to exhibit beneficial effects in this malignancy through regulation of a cohort of genes that overlap significantly with the NF-kB transcriptome. Here, it was examined whether or not the molecular mechanism could be attributed to modulation of NF-kB signaling using a combination of in vitro and in vivo models. Minocycline suppressed constitutive NF-kB activation in OVCAR-3 and SKOV-3 ovarian carcinoma cells and was correlated with attenuation of IkBa kinase (IKK) activation, IkBa phosphorylation and degradation, and p65 phosphorylation and nuclear translocation. The inhibition of IKK was found to be associated with suppression of TGF-b-activated-kinase-1 (TAK1) activation and its dissociation from TAK1-binding-protein-1 (TAB1), an indispensable functional mediator between TGF-b and TAK1. Further studies demonstrated that minocycline downregulated TGF-b1 expression. Enforced TGF-b1 expression induced NF-kB activity, and minocycline rescued this effect. Consistent with this finding, TGF-b1 knockdown suppressed NF-kB activation and abrogated the inhibitory effect of minocycline on this transcription factor. These results suggest that the minocycline-induced suppression of NF-kB activity is mediated, in part, through inhibition of TGF-b1. Furthermore, the influence of minocycline on NF-kB pathway activation was examined in female nude mice harboring intraperitoneal OVCAR-3 tumors. Both acute and chronic administration of minocycline led to suppression of p65 phosphorylation and nuclear translocation accompanied by downregulation of NF-kB activity and endogenous protein levels of its target gene products. These data reveal the therapeutic potential of minocycline as an agent targeting the pro-oncogenic TGF-b-NF-kB axis in ovarian cancer.

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“…In particular, the phosphorylation of residues Thr-184 and Thr-187 located at the TAK1 kinase domain is required for TAK1 kinase activity (10,11). However, a few researchers have suggested that the phosphorylation of TAK1 Thr-187 is insufficient for its activation (12)(13)(14)(15). Thus, additional post-transla-tional modifications are needed.…”

Section: Tgf-␤-activated Kinase 1 (Tak1) Is a Key Kinase In Mediatingmentioning

confidence: 99%

Transforming Growth Factor (TGF)-β-activated Kinase 1 (TAK1) Activation Requires Phosphorylation of Serine 412 by Protein Kinase A Catalytic Subunit α (PKACα) and X-linked Protein Kinase (PRKX)

Ouyang

Nie

et al. 2014

Journal of Biological Chemistry

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Background: Understanding of molecular mechanism of TAK1 activation is incomplete. Results: PKAC␣ and PRKX phosphorylate TAK1 at serine 412 to regulate TAK1 activation in the IL-1 receptor (IL-1R) and Toll-like receptor (TLR) signaling pathways. Conclusion: TAK1 activation requires phosphorylation by PKAC␣ and PRKX. Significance: This study advanced our understanding of the molecular mechanism of TAK1 activation.

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TAK1–TAB1 fusion protein: a novel constitutively active mitogen-activated protein kinase kinase kinase that stimulates AP-1 and NF-κB signaling pathways

Cited by 78 publications

References 24 publications

Critical Roles of Threonine 187 Phosphorylation in Cellular Stress-induced Rapid and Transient Activation of Transforming Growth Factor-β-activated Kinase 1 (TAK1) in a Signaling Complex Containing TAK1-binding Protein TAB1 and TAB2

Critical Roles of Threonine 187 Phosphorylation in Cellular Stress-induced Rapid and Transient Activation of Transforming Growth Factor-β-activated Kinase 1 (TAK1) in a Signaling Complex Containing TAK1-binding Protein TAB1 and TAB2

RETRACTED: Minocycline Targets the NF-κB Nexus through Suppression of TGF-β1-TAK1-IκB Signaling in Ovarian Cancer

Transforming Growth Factor (TGF)-β-activated Kinase 1 (TAK1) Activation Requires Phosphorylation of Serine 412 by Protein Kinase A Catalytic Subunit α (PKACα) and X-linked Protein Kinase (PRKX)

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