Recombinant human mitogen-activated protein kinase kinase 6 (MKK6), active, 20 µg

Background: MKK6 is a dual specificity kinase belonging to the group of MAP kinase kinase (MKKs).  MKKs are one part of three-kinase phosphorelay system “MAPK cascade” that converts extra cellular stimuli into various cellular responses such as gene expression, mitosis, and differentiation, proliferation, and cell survival/apoptosis.
Upon phosphorylation by MKKKs (e.g. MLKs, ASK1, TAK1) MKK6 is activated and able to phosphorylate the Thr–Gly–Tyr motif in the activation loop of p38α, p38β, p38γ and p38δ. MKK6, a closely related MKK serves also as activator of p38 MAPK. The activation of the  p38MAPKs by one or more MKK is stimulus-specific and cell specific. Whereas MKK3 seems to be the major activator of p38 in mesangial cells, MKK6 appears to be the predominant isoform in thymocytes. In contrast, both kinases are needed for full p38α activation in response to stimulation by TNFα. Upon UV irradiation, p38α is activated by MKK3, MKK6 and MKK4, which has also a minor contribution for p38α activity. Upon UV irradiation, p38α is activated by MKK3, MKK6 and MKK4, which triggers the stress-activated protein kinases, JNK and has also a minor contribution p38α activity. Whereas MKK6 can phosphorylate all four p38 MAPK family members, MKK3 activates p38α, p38γ and p38δ, but not  p38β.
Furthermore, LRRK2 (leucine-rich repeat kinase 2) a Parkinson\'s disease-related protein, binds to MKK3, -4, -6 and -7, suggesting a role of LRRK2 in the p38 and JNK pathway. Interaction of LRRK2 and MKKs stimulates expression and membrane translocation of these proteins, but does not strongly increase their phosphorylation level.

Recombinant human MKK6 (mitogen activated kinase kinase 6), GST-fusion protein, active enzyme, suitable for labeling MKK6 substrates

Expression system: E.coli    
Molecular weight: 63.6 kDa        
Protein concentration: 1.75 mg/ml (Bradford with BSA as standard)      
Storage buffer: 50 mM Tris-HCl, 150 mM NaCl, 0.1 mM EGTA, 1 mM DTT, 270 mM sucrose, pH 7.5
Purity: > 90% by SDS PAGE
Specific activity: 162,000 U*/mg (1 Unit is defined as the amount of MKK6 which activates unactive p38alpha/SAPK2a (0.5 mg/ml) by 1 U/min using 125 µM ATP at 30 °C. 1 U p38alpha/SAPK2a activity is defined as1 pmol phosphate transferred to myelin basic protein per min at 30 °C)
Entrez Gene ID: 5608 
UniProtKB: P52564

Ordering information: shipped on dry ice conditions 

Product specific literature:

Zhu X, Rottkamp CA, Hartzler A, Sun Z, Takeda A, Boux H, Shimohama S, Perry G, Smith MA.. (2001) „Activation of MKK6, an upstream activator of p38, in Alzheimer's disease.” J. Neurochem. 79(2):311-8.
 
Raingeaud J, Whitmarsh AJ, Barrett T, Derijard B, Davis RJ. (1996) " MKK3- and MKK6-regulated gene expression is mediated by the p38 mitogen-activated protein kinase signal transduction pathway. " Mol Cell Biol. 16(3):1247-55.
 
Chabaud-Riou M, Firestein GS. (1998) „Expression and activation of mitogen-activated protein kinase kinases-3 and -6 in rheumatoid arthritis.“ Am. J. Pathol. 164(1):177-84.

Product Citations:

Brichkina A, Nguyen NT, Baskar R, Wee S, Gunaratne J, Robinson RC, Bulavin DV. (2016) "Proline isomerisation as a novel regulatory mechanism for p38MAPK activation and functions." Cell Death Differ. 23(10):1592-601.