Summary

Name MAP2K6
Full Name Dual specificity mitogen-activated protein kinase kinase 6
Synonyms MAP kinase kinase 6, MAPKK 6, MAPK/ERK kinase 6, MEK 6, Stress-activated protein kinase kinase 3, SAPK kinase 3, SAPKK-3, SAPKK3 | MEK6, MKK6, PRKMK6, SKK3
Primary ID P52564
Links - -
Type protein
Relations 31
Pathways COVID-19 Causal Network, FAP: BMP, FAP: TGF beta, Osteoblast: BMP, Osteoblast: TGF beta, P38 Signaling, P38 Signaling and Myogenesis, SAPK/JNK Signaling, SARS-CoV MAPK PERTURBATION, TGF-beta Signaling, Toll like receptors
Function Dual specificity protein kinase which acts as an essential component of the MAP kinase signal transduction pathway. With MAP3K3/MKK3, catalyzes the concomitant phosphorylation of a threonine and a tyrosine residue in the MAP kinases p38 MAPK11, MAPK12, MAPK13 and MAPK14 and plays an important role in the regulation of cellular responses to cytokines and all kinds of stresses. Especially, MAP2K3/MKK3 and MAP2K6/MKK6 are both essential for the activation of MAPK11 and MAPK13 induced by environmental stress, whereas MAP2K6/MKK6 is the major MAPK11 activator in response to TNF. MAP2K6/MKK6 also phosphorylates and activates PAK6. The p38 MAP kinase signal transduction pathway leads to direct activation of transcription factors. Nuclear targets of p38 MAP kinase include the transcription factors ATF2 and ELK1. Within the p38 MAPK signal transduction pathway, MAP3K6/MKK6 mediates phosphorylation of STAT4 through MAPK14 activation, and is therefore required for STAT4 activation and STAT4-regulated gene expression in response to IL-12 stimulation. The pathway is also crucial for IL-6-induced SOCS3 expression and down-regulation of IL-6-mediated gene induction; and for IFNG-dependent gene transcription. Has a role in osteoclast differentiation through NF-kappa-B transactivation by TNFSF11, and in endochondral ossification and since SOX9 is another likely downstream target of the p38 MAPK pathway. MAP2K6/MKK6 mediates apoptotic cell death in thymocytes. Acts also as a regulator for melanocytes dendricity, through the modulation of Rho family GTPases.

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Modifications Tables

Relations

Regulator Mechanism target score
+ up-regulates activity img/direct-activation.png phosphorylation, binding MAP2K6 0.627
Publications: 2 Organism: Homo Sapiens
Pathways:P38 Signaling
+ up-regulates activity img/direct-activation.png phosphorylation STAT4 0.348
Publications: 1 Organism: Mus Musculus
+ up-regulates activity img/direct-activation.png phosphorylation MAPK13 0.64
Publications: 3 Organism: In Vitro, Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation MAPK14 0.728
Publications: 5 Organism: Chlorocebus Aethiops, Homo Sapiens
Pathways:P38 Signaling, P38 Signaling and Myogenesis, TGF-beta Signaling, Toll like receptors
+ up-regulates img/direct-activation.png phosphorylation MAPK12 0.639
Publications: 2 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation MAP2K6 0.427
Publications: 1 Organism: Homo Sapiens
Pathways:COVID-19 Causal Network, SAPK/JNK Signaling, SARS-CoV MAPK PERTURBATION, Toll like receptors
+ up-regulates activity img/direct-activation.png phosphorylation HSF4 0.2
Publications: 1
+ up-regulates img/direct-activation.png phosphorylation PAK6 0.2
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation MAP2K6 0.636
Publications: 2 Organism: Homo Sapiens
Pathways:P38 Signaling
+ up-regulates img/direct-activation.png phosphorylation MAPK13 0.64
Publications: 2 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png p38 0.728
Publications: 2 Organism: Chlorocebus Aethiops, Homo Sapiens
Pathways:COVID-19 Causal Network, SARS-CoV MAPK PERTURBATION
+ up-regulates activity img/direct-activation.png phosphorylation MAP2K6 0.2
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, Toll like receptors
+ up-regulates img/direct-activation.png phosphorylation CRK 0.2
Publications: 1 Organism: Homo Sapiens
Pathways:SAPK/JNK Signaling
+ up-regulates img/direct-activation.png phosphorylation MAPK11 0.684
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation MAPK10 0.438
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation MAP2K6 0.748
Publications: 2 Organism: Homo Sapiens
Pathways:COVID-19 Causal Network, P38 Signaling, P38 Signaling and Myogenesis, SAPK/JNK Signaling, SARS-CoV MAPK PERTURBATION, TGF-beta Signaling, Toll like receptors
+ up-regulates activity img/direct-activation.png phosphorylation MAP2K6 0.592
Publications: 1 Organism: Homo Sapiens
Pathways:P38 Signaling, P38 Signaling and Myogenesis
+ up-regulates img/indirect-activation.png MAP2K6 0.405
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation MAPK9 0.447
Publications: 1 Organism: Homo Sapiens