Recombinant human mitogen-activated protein kinase kinase 6 (MKK6), unactive, 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), unactive enzyme, protein is not phosphorylated and activated by MKKKs. Suitable as substrate for use in kinase activity assays, for kinase binding assays and for western blot analyses.

Expression system: E.coli    
Molecular weight: 38.9 kDa        
Protein concentration: 0.151 mg/ml (A280nm, 1Abs= 1mg/ml)   
Storage buffer: 10 mM Hepes, 150 mM NaCl, 20% glycerol, pH 7.4
Purity: > 95 % (The protein migrates as dimer with a molecular weight of 63 kDa verified by SEC).

Entrez Gene ID: 5608 
UniProtKB: P52564

Ordering information: shipped on dry ice conditions 

Product specific literature

Remy G, Risco AM, Iñesta-Vaquera FA, González-Terán B, Sabio G, Davis RJ, Cuenda A. (2010) “Differential activation of p38MAPK isoforms by MKK6 and MKK3.” Cell Signal. 22(4):660-7.

Cuenda A, Rousseau S. (2007) „ p38 MAP-kinases pathway regulation, function and role in human diseases.“ Biochim Biophys Acta, 1773(8):1358-75.

N. Tanaka, M. Kamanaka, H. Enslen, C. Dong, M.Wysk, R.J. Davis, R.A.Flavell,(2002) “Differential involvement of p38 mitogen-activated protein kinase kinases MKK3 and MKK6 in T-cell apoptosis” EMBO Rep. 3 785–791.

Hsu CH, Chan D, Wolozin B. (2010) “LRRK2 and the stress response: interaction with MKKs and JNK-interacting proteins.” Neurodegener Dis. 2010;7(1-3):68-75.

 Hsu CH, Chan D, Greggio E, Saha S, Guillily MD, Ferree A, Raghavan K, Shen GC, Segal L, Ryu H, Cookson MR, Wolozin B.(2010) “MKK6 binds and regulates expression of Parkinson's disease-related protein LRRK2.” J Neurochem.112(6):1593-604.