MEKK2 (also known as mitogen-activated protein kinase (MAPK) kinase kinase 2) is a major upstream activator of the JNK/MAPK cascade (1). MEKK2 can mediate in vitro phosphorylation of MKK4 and MKK7 which are key MAPKs that activate JNK. In addition, MEKK2 immunoprecipitates activated JUN in an IL1-dependent manner. Rheumatoid arthritis and osteoarthritis synovial tissues show high levels of MEKK2 indicating that it may be an important activator of the JNK pathway in arthritis (2). Endogenous MEKK2 is localized mainly in the cytosol of unstimulated cells.
1. Blank, J. L. et al: Molecular cloning of mitogen-activated protein/ERK kinase kinases (MEKK) 2 and 3: regulation of sequential phosphorylation pathways involving mitogen-activated protein kinase and c-Jun kinase. J. Biol. Chem. 271: 5361-5368, 1996.
2. Hammaker, D. R.; Boyle, D. L.; Chabaud-Riou, M.; Firestein, G. S. : Regulation of c-Jun N-terminal kinase by MEKK-2 and mitogen-activated protein kinase kinase kinases in rheumatoid arthritis. J. Immun. 172: 1612-1618, 2004.
Sample Kinase Activity Plot. For specific information on a given lot, see related technical data sheet.
Sample Purity Data. For specific information on a given lot, see related technical data sheet.
Storage, Stability and Shipping:
Store product at –70oC. For optimal storage, aliquot target into smaller quantities after centrifugation and store at recommended temperature. For most favorable performance, avoid repeated handling and multiple freeze/thaw cycles.
Natsuo Takeda Armelle et al., Ubiquitin-dependent regulation of MEKK2/3-MEK5-ERK5 signaling module by XIAP and cIAP1 EMBO Journal August 2014 10.15252/embj.201487808
Enomoto A et al., Prevention of calpain-dependent degradation of STK38 by MEKK2-mediated phosphorylation Scientific Reports November 2019 10.1038/s41598-019-52435-8
Kahle Michael et al., Interaction with the Paxillin LD1 Motif Relieves MEKK2 Auto-inhibition Journal of Molecular Signaling October 2015 10.5334/1750-2187-10-4
Ahmad Syed et al., Development and Validation of a High-Throughput Intrinsic ATPase Activity Assay for the Discovery of MEKK2 Inhibitors Journal of Biomolecular Screening April 2013 10.1177/1087057112466430
Apoptosis/Autophagy, ERK/MAPK Pathway, Invasion/Metastasis, JNK/SAPK Pathway, p38 Pathway, Ser/Thr Kinases