JNK regulates matrix metalloproteinase (MMP) gene expression and joint destruction in rheumatoid arthritis (RA). Previous studies demonstrated that the 2 upstream MAPK kinases (MKK-4 and MKK-7) are phosphorylated in RA synovium and form a complex with JNK in fibroblast-like synoviocytes (FLS). However, the functional hierarchy of MKK-4 and MKK-7 in FLS has not been determined. We determined the relative contributions of these MKKs by evaluating the effect of MKK-4 and MKK-7 gene knockdown in cultured FLS.
Division of Rheumatology, Allergy and Immunology, University of California, San Diego School of Medicine, 9500 Gilman Drive, La Jolla, CA 92093-0656, USA.
