|Other Names||Mitogen-activated protein kinase kinase kinase 4, MAP three kinase 1, MAPK/ERK kinase kinase 4, MEK kinase 4, MEKK 4, MAP3K4, KIAA0213, MAPKKK4, MEKK4, MTK1|
|Format||Synthetic peptide was lyophilized with 100% acetonitrile and is supplied as a powder. Reconstitute with 0.1 ml DI water for a final concentration of 1 mg/ml.|
|Storage||Maintain refrigerated at 2-8°C for up to 6 months. For long term storage store at -20°C.|
|Precautions||This product is for research use only. Not for use in diagnostic or therapeutic procedures.|
|Synonyms||KIAA0213, MAPKKK4, MEKK4, MTK1|
|Function||Component of a protein kinase signal transduction cascade. Activates the CSBP2, P38 and JNK MAPK pathways, but not the ERK pathway. Specifically phosphorylates and activates MAP2K4 and MAP2K6.|
|Cellular Location||Cytoplasm, perinuclear region. Note=Localized in perinuclear vesicular-like structures, probably Golgi-associated vesicles.|
|Tissue Location||Expressed at high levels in heart, placenta, skeletal muscle and pancreas, and at lower levels in other tissues.|
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The central core of each mitogen-activated protein kinase(MAPK) pathway is a conserved cascade of 3 protein kinases: anactivated MAPK kinase kinase (MAPKKK) phosphorylates and activatesa specific MAPK kinase (MAPKK), which then activates a specificMAPK. While the ERK MAPKs are activated by mitogenic stimulation,the CSBP2 and JNK MAPKs are activated by environmental stressessuch as osmotic shock, UV irradiation, wound stress, andinflammatory factors. This gene encodes a MAPKKK, the MEKK4protein, also called MTK1. This protein contains a protein kinasecatalytic domain at the C terminus. The N-terminal nonkinase domainmay contain a regulatory domain. Expression of MEKK4 in mammaliancells activated the CSBP2 and JNK MAPK pathways, but not the ERKpathway. In vitro kinase studies indicated that recombinant MEKK4can specifically phosphorylate and activate PRKMK6 and SERK1,MAPKKs that activate CSBP2 and JNK, respectively but cannotphosphorylate PRKMK1, an MAPKK that activates ERKs. MEKK4 is amajor mediator of environmental stresses that activate the CSBP2MAPK pathway, and a minor mediator of the JNK pathway. Twoalternatively spliced transcripts encoding distinct isoforms havebeen described.
Grucza, R.A., et al. Addict Biol 15(3):346-357(2010)Whitmarsh, A.J., et al. Oncogene 26(22):3172-3184(2007)Aissouni, Y., et al. Biochem. Biophys. Res. Commun. 338(2):808-814(2005)Abell, A.N., et al. J. Biol. Chem. 280(43):35793-35796(2005)Derbyshire, Z.E., et al. Mol. Cell. Biochem. 271 (1-2), 77-90 (2005) :
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