Phosphorylation‐dependent activation of TAK1 mitogen‐activated protein kinase kinase kinase by TAB1

  title={Phosphorylation‐dependent activation of TAK1 mitogen‐activated protein kinase kinase kinase by TAB1},
  author={Hiroaki Sakurai and Hidetaka Miyoshi and Junko Mizukami and Takahisa Sugita},
  journal={FEBS Letters},

Protein Phosphatase 6 Down-regulates TAK1 Kinase Activation in the IL-1 Signaling Pathway*

It is found that toxin inhibition of type 2A protein phosphatases greatly enhances interleukin 1 (IL-1)-dependent phosphorylation of Thr-187 in the TAK1 activation loop as well as the catalytic activity of Tak1.

Autoactivation of Transforming Growth Factor β-activated Kinase 1 Is a Sequential Bimolecular Process*

A bacterial expression system is established to generate recombinant mammalian TAK1 complexes and a model for the chronological order of events governing TAB1-induced Tak1 autoactivation is presented.

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)*

This work shows that the Thr-187 phosphorylation of TAK1 is regulated by its C-terminal coiled-coil domain-mediated dimerization in an autophosphorylation manner, which unravels a previously unknown mechanism involving Tak1 phosphorylated mediated by PKACα and PRKX that contributes to innate immune signaling.

TAB4 Stimulates TAK1-TAB1 Phosphorylation and Binds Polyubiquitin to Direct Signaling to NF-κB*

The results show that TAB4 binds TAK1 and polyubiquitin chains to promote specific sites of phosphorylation in TAK 1-TAB1, which activates IKK signaling to NF-κB.

Post-Translational Modifications of the TAK1-TAB Complex

Recent advances in the understanding of the post-translational modifications (PTMs) of the TAK1-TAB complex are focused on.

Phosphorylation of Thr-178 and Thr-184 in the TAK1 T-loop Is Required for Interleukin (IL)-1-mediated Optimal NFκB and AP-1 Activation as Well as IL-6 Gene Expression*

This finding is the first report that substitution of key serine/threonine residues with acidic residues mimics the phosphorylated state of TAK1 and renders Tak1 active during its induced activation.

TAK1 mediates convergence of cellular signals for death and survival

This review highlights how TAK1 orchestrates regulation of energy homeostasis via AMPK and its emerging role in influencing mTORC1 pathway to regulate death or survival in tandem.

Polyubiquitination of Transforming Growth Factor β-activated Kinase 1 (TAK1) at Lysine 562 Residue Regulates TLR4-mediated JNK and p38 MAPK Activation

A feedback loop for phosphorylation and ubiquitination of TAK1 is demonstrated, indicating a dynamic regulation between TAK 1 polyubiquitiantion and phosphorylated activation, and the molecular mechanism by which IKK and MAPKs are differentially activated in the TLR4 pathway.



TAK1 Mitogen-activated Protein Kinase Kinase Kinase Is Activated by Autophosphorylation within Its Activation Loop*

Ex vivo TAK1 is constitutively associated with TAB1 and phosphorylated following IL-1 stimulation and mutation to alanine of a conserved serine residue (Ser-192) in the activation loop between kinase domains VII and VIII abolishes both phosphorylation and activation of TAK 1.

TAB1: An Activator of the TAK1 MAPKKK in TGF-β Signal Transduction

Overproduction of TAB1 enhanced activity of the plasminogen activator inhibitor 1 gene promoter, which is regulated by TGF-β, and increased the kinase activity of TAK1.

A Novel Kinase Cascade Mediated by Mitogen-activated Protein Kinase Kinase 6 and MKK3*

Results indicate the existence of a novel kinase cascade consisting of TAK1, MAPKK6/MKK3, and p38/MPK2, and could be demonstrated to be phosphorylated and activated in vitro by TAKING1, a recently identified MAPKK kinase.

TAK1 Mediates the Ceramide Signaling to Stress-activated Protein Kinase/c-Jun N-terminal Kinase*

Results indicate that TAK1 may function as a mediator of ceramide signaling to SAPK/JNK activation, and suggest that the ceramide/SAPK/ JNK signaling pathway is required for stress-induced apoptosis.

Identification of a Member of the MAPKKK Family as a Potential Mediator of TGF-β Signal Transduction

Results suggest that TAK1 functions as a mediator in the signaling pathway of TGF-β superfamily members.

Functional Interactions of Transforming Growth Factor β-activated Kinase 1 with IκB Kinases to Stimulate NF-κB Activation*

Results demonstrated a novel signaling pathway to NF-κB activation through TAK1 in which Taker1 may act as a regulatory kinase of IKKs, and the kinase-negative TAK2 acted as a dominant negative inhibitor against tumor necrosis factor-α-induced NF-kkB activation.

Activation of the Hematopoietic Progenitor Kinase-1 (HPK1)-dependent, Stress-activated c-Jun N-terminal Kinase (JNK) Pathway by Transforming Growth Factor β (TGF-β)-activated Kinase (TAK1), a Kinase Mediator of TGF β Signal Transduction*

TAK1 is identified as a regulator in the HPK1 → TAK1 → MKK4/SEK1→ JNK kinase cascade and the involvement of JNK in the TGF-β signaling pathway is indicated.

MKK3- and MKK6-regulated gene expression is mediated by the p38 mitogen-activated protein kinase signal transduction pathway

Cotransfection experiments demonstrated that p38 MAP kinase activation causes increased reporter gene expression mediated by the transcription factors ATF2 and Elk-1, demonstrating that the nucleus is one target of the p38MAP kinase signal transduction pathway.

The kinase TAK1 can activate the NIK-IκB as well as the MAP kinase cascade in the IL-1 signalling pathway

It is shown that the MAPKK kinase TAK1 acts upstream of NIK in the IL-1-activated signalling pathway and that TAK 1 associates with TRAF6 during IL- 1 signalling, which indicates that Taker1 links TRAf6 to the NIK–IKK cascade in theIL-1 signalling pathway.