activated human TAK1 phosphorylates MKK3/MKK6

Stable Identifier
R-HSA-450346
Type
Reaction [transition]
Species
Homo sapiens
Compartment
Locations in the PathwayBrowser
General
SVG |   | PPTX  | SBGN
Click the image above or here to open this reaction in the Pathway Browser
The layout of this reaction may differ from that in the pathway view due to the constraints in pathway layout

Human MKK3 (MAP2K4) and MKK6 (MAP2K6) are two closely related dual-specificity protein kinases. Both are activated by cellular stress and inflammatory cytokines, and both phosphorylate and activate p38 MAP kinase at its activation site Thr-Gly-Tyr but do not phosphorylate or activate Erk1/2 or SAPK/JNK.

Activation of MKK3 and MKK6 occurs through phosphorylation of serine and threonine residues at the typical Ser-Xaa-Ala-Xaa-Thr motif in their activation loop. Residues involved into these protein kinases activation correspond to human sites Ser189 and Thr193 for MKK3 and Ser207 and Thr211 for MKK6 .

Literature References
PubMed ID Title Journal Year
15837794 Simultaneous blockade of NFkappaB, JNK, and p38 MAPK by a kinase-inactive mutant of the protein kinase TAK1 sensitizes cells to apoptosis and affects a distinct spectrum of tumor necrosis factor [corrected] target genes

Thiefes, A, Wolter, S, Mushinski, JF, Hoffmann, E, Dittrich-Breiholz, O, Graue, N, Dörrie, A, Schneider, H, Wirth, D, Luckow, B, Resch, K, Kracht, M

J Biol Chem 2005
8622669 MKK3- and MKK6-regulated gene expression is mediated by the p38 mitogen-activated protein kinase signal transduction pathway

Raingeaud, J, Whitmarsh, AJ, Barrett, T, Derijard, B, Davis, RJ

Mol Cell Biol 1996
8533096 Identification of a member of the MAPKKK family as a potential mediator of TGF-beta signal transduction

Yamaguchi, K, Shirakabe, K, Shibuya, H, Irie, K, Oishi, I, Ueno, N, Taniguchi, T, Nishida, E, Matsumoto, K

Science 1995
16186825 Essential function for the kinase TAK1 in innate and adaptive immune responses

Sato, S, Sanjo, H, Takeda, K, Ninomiya-Tsuji, J, Yamamoto, M, Kawai, T, Matsumoto, K, Takeuchi, O, Akira, S

Nat Immunol 2005
Participants
Participant Of
Catalyst Activity
Catalyst Activity
Title
MAP kinase kinase kinase activity of Activated TAK complexes [cytosol]
Physical Entity
Activity
Orthologous Events
Authored
Reviewed
Created