The Function of MAP2K6
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.
Protein names
Recommended name:
Dual specificity mitogen-activated protein kinase kinase 6Short name:
MEK 6Alternative name(s):
MAP kinase kinase 6MAPKK 6
MAPK/ERK kinase 6
Stress-activated protein kinase kinase 3
SAPK kinase 3
SAPKK-3
SAPKK3
- RS817565 (MAP2K6) ??
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Top Gene-Substance Interactions
MAP2K6 Interacts with These Diseases
| Disease | Score |
Substances That Increase MAP2K6
| Substances | Interaction | Organism | Category |
Substances That Decrease MAP2K6
| Substances | Interaction | Organism | Category |
Conditions with Increased Gene Activity
| Condition | Change (log2fold) | Comparison | Species | Experimental variables | Experiment name |
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Conditions with Decreased Gene Activity
| Condition | Change (log2fold) | Comparison | Species | Experimental variables | Experiment name |
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Technical
The following transcription factors affect gene expression:
Tissue specificity:
Isoform 2 is only expressed in skeletal muscle. Isoform 1 is expressed in skeletal muscle, heart, and in lesser extent in liver or pancreas.
Gene Pathways:
Induction:
Strongly activated by UV, anisomycin, and osmotic shock but not by phorbol esters, NGF or EGF.
Enzyme Regulation:
Activated by dual phosphorylation on Ser-207 and Thr-211 in response to a variety of cellular stresses, including UV radiation, osmotic shock, hypoxia, inflammatory cytokines, interferon gamma (IFNG), and less often by growth factors. MAP2K6/MKK6 is activated by the majority of M3Ks, such as MAP3K5/ASK1, MAP3K1/MEKK1, MAP3K2/MEKK2, MAP3K3/MEKK3, MAP3K4/MEKK4, MAP3K7/TAK1, MAP3K11/MLK3 and MAP3K17/TAOK2.
Molecular Function:
- Signal Transducer, Downstream Of Receptor, With Serine/Threonine Kinase Activity
- Map Kinase Kinase Activity
- Protein Tyrosine Kinase Activity
- Atp Binding
- Protein Kinase Binding
Biological Processes:
- Activation Of Mapk Activity
- Response To Ischemia
- Transcription, Dna-Templated
- Regulation Of Transcription, Dna-Templated
- Apoptotic Process
- Dna Damage Induced Protein Phosphorylation
- Cell Cycle Arrest
- Signal Transduction
- Ovulation Cycle Process
- Positive Regulation Of Prostaglandin Secretion
- Proteolysis In Other Organism
- Positive Regulation Of Apoptotic Process
- Positive Regulation Of Nitric-Oxide Synthase Biosynthetic Process
- Cardiac Muscle Contraction
- Nucleotide-Binding Oligomerization Domain Containing Signaling Pathway
- Cellular Response To Sorbitol