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Lead Time
Basically, we can dispatch the products out in 1-3 working days after receiving your orders. Delivery time maybe differs from different purchasing way or location, please kindly consult your local distributors for specific delivery time.
Note: All of our proteins are default shipped with normal blue ice packs, if you request to ship with dry ice, please communicate with us in advance and extra fees will be charged.
Usage
For Research Use Only. Not for use in diagnostic or therapeutic procedures.
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.
Gene References into Functions
Data show that miR-625-3p induces oxaliplatin resistance by abrogating MAP2K6-p38-regulated apoptosis and cell cycle control networks.PMID:27526785
acts as a repressor of UCP1 expression, suggesting that its inhibition promotes adipose tissue browning and increases organismal energy expenditurePMID:29021624
Data indicate that mitogen-activated protein kinase kinase 6 (MKK6) levels were substantially higher in monocytes than in neutrophils.PMID:25214442
Data show significant increase in the expression of MKK6 in Esophageal, Stomach, and Colon cancers as compared to controls.PMID:25019214
uncover a new mechanism of deactivation of MKK6-p38 and substantiate a novel regulatory role of FBXO31 in stress responsePMID:24936062
Serine phosphorylation of p66shc is carried out by active MKK6. beta-Amyloid-induced ROS production and apoptosis increased in the presence of MKK6 and p66shc, which directly associate.PMID:24085465
The models confirmed the reaction order, revealed processivity in the phosphorylation of MEK6 by ASK1, and suggested that the order of phosphorylation is dictated by both binding and catalysis rates.PMID:23744074
crystal structure of human non-phosphorylated MAP2K6 (npMAP2K6) complexed with an ATP analogue was determined at 2.6 A resolution and represents an auto-inhibition state of MAP2K6PMID:22383536
activation by mechanical stretch induces HMGB1 and cytokine expression in A549 cellsPMID:21926646
Results suggest that the p38alpha, MAPK, and MKK6 play prominent roles in IL-1beta and C/EBP-beta-mediated C3 gene expression in astrocytes.PMID:21308746
Impaired cytokine production in natural killer (NK)T cells is demonstrated from MKK3-deficient6+/- mice.PMID:21368234
we demonstrated that MKK6 has a role for regulation of dendricity in melanocytes.PMID:20869211
MKK6 and other MAP2Ks are a distinct class of cellular redox sensorsPMID:21078955
MKK6 p38 alpha signaling pathway regulates the expression of RAGE induced by mechanical stretch in A549 cells.PMID:19846005
Mechanism of oxidative stress-induced ASK1-catalyzed MKK6 phosphorylation.(PMID:20364819
active MKK6 in HepG2 cells enhanced basal activity or IL-6-induced transcriptional activation of a SOCS3 promoterPMID:11727828
MKK6 is involved in a positive feedback loop regulating macrophage signaling with p38 MAP kinasePMID:12509443
PAK6 kinase activity was repressed by a p38 mitogen-activated protein (MAP) kinase antagonist and could be strongly stimulated by constitutively active MAP kinase kinase 6 (MKK6)PMID:15550393
MKK6 promotes the development of cardiomyopathy by activation of a kinase cascadePMID:15722372
MEK6E activates p38 and results in phosphorylation of its downstream substrate, heat shock protein 27PMID:15790570
selectivity pocket compounds prevent MKK6-dependent activation of p38alpha in addition to inhibiting catalysis by activated p38alphaPMID:16342939
findings show that Yersinia YopJ acted as an acetyltransferase, using acetyl-coenzyme A (CoA) to modify the critical serine and threonine residues in the activation loop of MAPKK6 and thereby blocking phosphorylationPMID:16728640
Conditional induction of a dominant active form of MAPK kinase 6, a direct upstream kinase of p38, in Langerhans cells induces up-regulation of costimulatory molecules & enhances their T-cell stimulatory capacity.PMID:16960152
Data suggest that sequence variations of ASK1 and MAP2K6 lead to partially sex-specific changes in the levels and/or phosphorylation states of p38 and p38-regulated proteins that might contribute to the observed delaying effects in the age of onset of HD.PMID:18327563
Gel filtration and small-angle X-ray scattering analysis confirm that the crystallographically observed ellipsoidal dimer is a feature of MEK6/DeltaN/DD and full-length unphosphorylated wild-type MEK6 in solutionPMID:19141286
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Subcellular Location
Nucleus. Cytoplasm. Cytoplasm, cytoskeleton. Note=Binds to microtubules.
Protein Families
Protein kinase superfamily, STE Ser/Thr protein kinase family, MAP kinase kinase subfamily
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.