MEKK2 (also known as mitogen-activated protein kinase (MAPK) kinase kinase 2) is a major upstream activator of the JNK/MAPK cascade. 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. Endogenous MEKK2 is localized mainly in the cytosol of unstimulated cells.
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