MKK6 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. Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. MAP kinase kinase subfamily. Isoform 2 is only expressed in skeletal muscle. Isoform 1 is expressed in skeletal muscle, heart, and in lesser extent in liver or pancreas. 2 alternatively spliced human isoforms have been reported. Note: This description may include information from UniProtKB.
Protein type: EC 2.7.12.2; Kinase, protein; Protein kinase, STE; Protein kinase, dual-specificity (non-receptor); STE group; STE7 family
Chromosomal Location of Human Ortholog: 11|11 E1-E2
Cellular Component:  cytoplasm; cytoskeleton; cytosol; nucleus
Molecular Function:  ATP binding; identical protein binding; kinase activity; MAP kinase kinase activity; nucleotide binding; protein binding; protein kinase activity; protein kinase binding; protein serine/threonine kinase activity; protein tyrosine kinase activity; transferase activity
Biological Process:  activation of MAPK activity; activation of protein kinase activity; apoptotic process; cardiac muscle contraction; MAPK cascade; negative regulation of cold-induced thermogenesis; phosphorylation; positive regulation of apoptotic process; positive regulation of nitric-oxide synthase biosynthetic process; positive regulation of prostaglandin secretion; positive regulation of protein phosphorylation; protein phosphorylation; signal transduction by protein phosphorylation; stress-activated protein kinase signaling cascade
Reference #:  P70236 (UniProtKB)
Alt. Names/Synonyms: Dual specificity mitogen-activated protein kinase kinase 6; MAP kinase kinase 6; Map2k6; MAPK/ERK kinase 6; MAPKK 6; MAPKK6; MEK 6; MEK6; mitogen activated protein kinase kinase 6; mitogen-activated protein kinase kinase 6; MKK6; MP2K6; OTTMUSP00000003317; Prkm; Prkmk6; protein kinase, mitogen activated, kinase 6; SAP; SAPKK3
Gene Symbols: Map2k6
Molecular weight: 37,432 Da
Basal Isoelectric point: Predict pI for various phosphorylation states
CST Pathways:  Actin Dynamics  |  B Cell Receptor Signaling  |  ErbB/HER Signaling  |  GPCR Signaling to MAPKs  |  IL6 Signaling  |  Regulation of P38 MAPKs  |  TGF-ß Signaling  |  Toll-Like Receptor Signaling
Protein-Specific Antibodies, siRNAs or Recombinant Proteins from Cell Signaling Technology® Total Proteins
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MKK6

Protein Structure Not Found.


Cross-references to other databases:  STRING  |  Reactome  |  BioGPS  |  KinBase  |  Pfam  |  ENZYME  |  Phospho.ELM  |  NetworKIN  |  UniProtKB  |  Entrez-Gene  |  Ensembl Gene