Summary

Name MAP2K4
Full Name Dual specificity mitogen-activated protein kinase kinase 4
Synonyms MAP kinase kinase 4, MAPKK 4, JNK-activating kinase 1, MAPK/ERK kinase 4, MEK 4, SAPK/ERK kinase 1, SEK1, Stress-activated protein kinase kinase 1, SAPK kinase 1, SAPKK-1, SAPKK1, c-Jun N-terminal kinase kinase 1, JNKK | JNKK1, MEK4, MKK4, PRKMK4, SEK1, SERK1, SKK1
Primary ID P45985
Links - -
Type protein
Relations 36
Pathways EGFR, P38 Signaling, P38 Signaling and Myogenesis, SAPK/JNK Signaling, TGFbeta Signaling, TNF alpha, Macrophage polarization
Function Dual specificity protein kinase which acts as an essential component of the MAP kinase signal transduction pathway. Essential component of the stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signaling pathway. With MAP2K7/MKK7, is the one of the only known kinase to directly activate the stress-activated protein kinase/c-Jun N-terminal kinases MAPK8/JNK1, MAPK9/JNK2 and MAPK10/JNK3. MAP2K4/MKK4 and MAP2K7/MKK7 both activate the JNKs by phosphorylation, but they differ in their preference for the phosphorylation site in the Thr-Pro-Tyr motif. MAP2K4 shows preference for phosphorylation of the Tyr residue and MAP2K7/MKK7 for the Thr residue. The phosphorylation of the Thr residue by MAP2K7/MKK7 seems to be the prerequisite for JNK activation at least in response to proinflammatory cytokines, while other stimuli activate both MAP2K4/MKK4 and MAP2K7/MKK7 which synergistically phosphorylate JNKs. MAP2K4 is required for maintaining peripheral lymphoid homeostasis. The MKK/JNK signaling pathway is also involved in mitochondrial death signaling pathway, including the release cytochrome c, leading to apoptosis. Whereas MAP2K7/MKK7 exclusively activates JNKs, MAP2K4/MKK4 additionally activates the p38 MAPKs MAPK11, MAPK12, MAPK13 and MAPK14.

Viewer

Modifications Tables

Relations

Regulator Mechanism target score
+ up-regulates img/direct-activation.png phosphorylation MAP2K4 0.76
Publications: 2 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation MAP2K4
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation MAP2K4
Publications: 2 Organism: In Vitro
Pathways:EGFR, Macrophage polarization, P38 Signaling, P38 Signaling and Myogenesis, SAPK/JNK Signaling, TNF alpha, TGFbeta Signaling
+ down-regulates img/direct_inhibition.png phosphorylation MAP2K4 0.14
Publications: 1 Organism: Homo Sapiens
Pathways:P38 Signaling and Myogenesis
+ down-regulates img/direct_inhibition.png phosphorylation MAP2K4
Publications: 1 Organism: Homo Sapiens
Pathways:EGFR
+ up-regulates activity img/direct-activation.png phosphorylation MAPK14 0.35
Publications: 2 Organism: Homo Sapiens
Pathways:P38 Signaling, P38 Signaling and Myogenesis, TNF alpha, TGFbeta Signaling
+ up-regulates activity img/direct-activation.png phosphorylation MAPK8
Publications: 3 Organism: Homo Sapiens, In Vitro
Pathways:EGFR, Macrophage polarization, SAPK/JNK Signaling, TNF alpha
+ up-regulates activity img/direct-activation.png phosphorylation MAP2K4 0.89
Publications: 2 Organism: Homo Sapiens
Pathways:EGFR, Macrophage polarization, SAPK/JNK Signaling, TNF alpha
+ up-regulates activity img/direct-activation.png phosphorylation MAP2K4 0.82
Publications: 2 Organism: Homo Sapiens
Pathways:P38 Signaling, P38 Signaling and Myogenesis, TNF alpha
+ up-regulates img/direct-activation.png phosphorylation MAPK9 0.75
Publications: 1 Organism: Homo Sapiens
Tissue: Breast, Prostate Gland
+ up-regulates activity img/direct-activation.png phosphorylation MAPK10 0.34
Publications: 1 Organism: In Vitro
+ up-regulates img/direct-activation.png phosphorylation MAPK10 0.34
Publications: 5 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png phosphorylation RXRA 0.23
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation MAP2K4 0.68
Publications: 1 Organism: Homo Sapiens
Pathways:P38 Signaling
+ up-regulates img/direct-activation.png binding MAP2K4
Publications: 1 Organism: Homo Sapiens
Pathways:SAPK/JNK Signaling
+ up-regulates activity img/direct-activation.png binding MAP2K4 0.61
Publications: 1 Organism: Homo Sapiens
Pathways:P38 Signaling
+ up-regulates img/direct-activation.png binding MAP2K4 0.60
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation MAP2K4 0.78
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png binding MAP2K4 0.39
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation MAP2K4
Publications: 1 Organism: Homo Sapiens
Pathways:P38 Signaling, P38 Signaling and Myogenesis, SAPK/JNK Signaling, TGFbeta Signaling
+ up-regulates img/direct-activation.png phosphorylation MAP2K4 0.49
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation JNK
Publications: 2 Organism: Homo Sapiens
Pathways:TGFbeta Signaling
+ up-regulates activity img/direct-activation.png phosphorylation MAP2K4 0.80
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png binding MAP2K4 0.63
Publications: 1 Organism: Homo Sapiens