MAP2K6

This gene encodes a member of the dual specificity protein kinase family, which functions as a mitogen-activated protein (MAP) kinase kinase. MAP kinases, also known as extracellular signal-regulated kinases (ERKs), act as an integration point for multiple biochemical signals. This protein phosphorylates and activates p38 MAP kinase in response to inflammatory cytokines or environmental stress. As an essential component of p38 MAP kinase mediated signal transduction pathway, this gene is involved in many cellular processes such as stress induced cell cycle arrest, transcription activation and apoptosis. [provided by RefSeq, Jul 2008]

Mitogen-Activated Protein Kinase Kinase 6

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.

Apoptotic processIEA:UniProtKB-KW
Bone developmentIEA:Ensembl
Cardiac muscle contractionIEA:Ensembl
Cellular response to sorbitolIEA:Ensembl
Cellular senescenceTAS:Reactome
DNA damage induced protein phosphorylationManual Assertion Based On ExperimentTAS:ProtInc
MAPK cascadeManual Assertion Based On ExperimentIDA:GO_Central
Negative regulation of cold-induced thermogenesisBy SimilarityISS:YuBioLab
Nucleotide-binding oligomerization domain containing signaling pathwayTAS:Reactome
Osteoblast differentiationIEA:Ensembl
Ovulation cycle processIEA:Ensembl
p38MAPK cascadeTAS:Reactome
Positive regulation of apoptotic processIEA:Ensembl
Positive regulation of MAP kinase activityIEA:Ensembl
Positive regulation of nitric-oxide synthase biosynthetic processIEA:Ensembl
Positive regulation of prostaglandin secretionIEA:Ensembl
Regulation of cell cycleManual Assertion Based On ExperimentTAS:ProtInc
Regulation of signal transduction by p53 class mediatorTAS:Reactome
Response to ischemiaIEA:Ensembl
Response to xenobiotic stimulusIEA:Ensembl
Signal transductionManual Assertion Based On ExperimentTAS:ProtInc
Stress-activated MAPK cascadeManual Assertion Based On ExperimentIDA:UniProtKB

Nucleus
Cytoplasm
Cytoplasm, cytoskeleton
Binds to microtubules.

Weakly autophosphorylated. Phosphorylated at Ser-207 and Thr-211 by the majority of M3Ks, such as MAP3K5/ASK1, MAP3K1/MEKK1, MAP3K2/MEKK2, MAP3K3/MEKK3, MAP3K4/MEKK4, MAP3K7/TAK1, MAP3K11/MLK3 and MAP3K17/TAOK2.
(Microbial infection) Acetylation of Ser-207 and Thr-211 by Yersinia YopJ prevents phosphorylation and activation, thus blocking the MAPK signaling pathway.