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 45
Pathways COVID-19 Causal Network, EGFR Signaling, Macrophage polarization, P38 Signaling, P38 Signaling and Myogenesis, SAPK/JNK Signaling, SARS-CoV MAPK PERTURBATION, SARS-CoV ATTACHMENT AND ENTRY, TNF-alpha Signaling, TGF-beta Signaling
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 activity img/direct-activation.png phosphorylation MAP2K4 0.2
Publications: 2 Organism: In Vitro
Pathways:COVID-19 Causal Network, EGFR Signaling, Macrophage polarization, P38 Signaling, P38 Signaling and Myogenesis, SAPK/JNK Signaling, SARS-CoV MAPK PERTURBATION, SARS-CoV ATTACHMENT AND ENTRY, TNF-alpha Signaling, TGF-beta Signaling
+ up-regulates activity img/direct-activation.png phosphorylation MAP2K4 0.605
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation MAP2K4 0.605
Publications: 2 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png phosphorylation MAP2K4 0.2
Publications: 1 Organism: Homo Sapiens
Pathways:COVID-19 Causal Network, EGFR Signaling
+ down-regulates img/direct_inhibition.png phosphorylation MAP2K4 0.577
Publications: 1 Organism: Homo Sapiens
Pathways:P38 Signaling and Myogenesis
+ up-regulates activity img/direct-activation.png phosphorylation MAPK13 0.432
Publications: 2 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation MAPK14 0.57
Publications: 2 Organism: Homo Sapiens
Pathways:P38 Signaling, P38 Signaling and Myogenesis, TNF-alpha Signaling, TGF-beta Signaling
+ up-regulates img/direct-activation.png phosphorylation MAPK9 0.712
Publications: 2 Organism: Homo Sapiens
Tissue: Breast, Prostate Gland
+ up-regulates activity img/direct-activation.png phosphorylation MAPK8 0.736
Publications: 3 Organism: Homo Sapiens, In Vitro
Pathways:COVID-19 Causal Network, EGFR Signaling, Macrophage polarization, SAPK/JNK Signaling, SARS-CoV ATTACHMENT AND ENTRY, TNF-alpha Signaling
+ up-regulates img/direct-activation.png phosphorylation MAPK10 0.728
Publications: 6 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation MAP2K4 0.712
Publications: 2 Organism: Homo Sapiens
Pathways:COVID-19 Causal Network, EGFR Signaling, Macrophage polarization, SAPK/JNK Signaling, SARS-CoV MAPK PERTURBATION, TNF-alpha Signaling
+ up-regulates activity img/direct-activation.png phosphorylation MAP2K4 0.612
Publications: 2 Organism: Homo Sapiens
Pathways:P38 Signaling, P38 Signaling and Myogenesis, TNF-alpha Signaling
+ up-regulates activity img/direct-activation.png phosphorylation MAPK10 0.728
Publications: 1 Organism: In Vitro
+ down-regulates img/direct_inhibition.png phosphorylation RXRA 0.2
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png binding MAP2K4 0.503
Publications: 1 Organism: Homo Sapiens
Pathways:COVID-19 Causal Network, SARS-CoV ATTACHMENT AND ENTRY
+ up-regulates activity img/direct-activation.png phosphorylation MAP2K4 0.545
Publications: 1 Organism: Homo Sapiens
Pathways:P38 Signaling
+ up-regulates img/direct-activation.png binding MAP2K4 0.615
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation MAP2K4 0.535
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation JNK 0.736
Publications: 3 Organism: Homo Sapiens
Pathways:COVID-19 Causal Network, SARS-CoV MAPK PERTURBATION, TGF-beta Signaling
+ up-regulates activity img/direct-activation.png binding MAP2K4 0.581
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png relocalization MAP2K4 0.2
Publications: 1 Organism: Mus Musculus
+ up-regulates activity img/indirect-activation.png MAP2K4 0.2
Publications: 1 Organism: Homo Sapiens
Pathways:COVID-19 Causal Network, SARS-CoV MAPK PERTURBATION, SARS-CoV ATTACHMENT AND ENTRY
+ up-regulates activity img/direct-activation.png phosphorylation p38 0.57
Publications: 1 Organism: Chlorocebus Aethiops
Pathways:COVID-19 Causal Network, SARS-CoV MAPK PERTURBATION
+ up-regulates activity img/direct-activation.png binding MAP2K4 0.264
Publications: 1 Organism: Homo Sapiens
Pathways:P38 Signaling
+ up-regulates activity img/direct-activation.png phosphorylation MAP2K4 0.2
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png binding MAP2K4 0.503
Publications: 1 Organism: Homo Sapiens
Pathways:COVID-19 Causal Network, SARS-CoV ATTACHMENT AND ENTRY
+ up-regulates activity img/direct-activation.png phosphorylation MAP2K4 0.589
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png binding MAP2K4 0.319
Publications: 1 Organism: Homo Sapiens
Pathways:SAPK/JNK Signaling
+ up-regulates activity img/direct-activation.png phosphorylation MAP2K4 0.692
Publications: 1 Organism: Homo Sapiens
Pathways:COVID-19 Causal Network, P38 Signaling, P38 Signaling and Myogenesis, SAPK/JNK Signaling, SARS-CoV MAPK PERTURBATION, TGF-beta Signaling