Nuclear accumulation of NFAT4 opposed by the JNK signal transduction pathway
Howard Hughes Medical Institute and Program in Molecular Medicine
Animals; Binding Sites; COS Cells; Calcineurin; Calcium-Calmodulin-Dependent Protein Kinases; Cell Line; Cell Nucleus; Cyclosporine; Cytoplasm; DNA-Binding Proteins; Humans; JNK Mitogen-Activated Protein Kinases; Jurkat Cells; Mitogen-Activated Protein Kinase Kinases; *Mitogen-Activated Protein Kinases; Mutation; NFATC Transcription Factors; *Nuclear Proteins; Phosphorylation; Protein Kinases; Recombinant Fusion Proteins; *Signal Transduction; T-Lymphocytes; Transcription Factors; Transcription, Genetic
Life Sciences | Medicine and Health Sciences
The nuclear factor of activated T cells (NFAT) group of transcription factors is retained in the cytoplasm of quiescent cells. NFAT activation is mediated in part by induced nuclear import. This process requires calcium-dependent dephosphorylation of NFAT caused by the phosphatase calcineurin. The c-Jun amino-terminal kinase (JNK) phosphorylates NFAT4 on two sites. Mutational removal of the JNK phosphorylation sites caused constitutive nuclear localization of NFAT4. In contrast, JNK activation in calcineurin-stimulated cells caused nuclear exclusion of NFAT4. These findings show that the nuclear accumulation of NFAT4 promoted by calcineurin is opposed by the JNK signal transduction pathway.
DOI of Published Version
Science. 1997 Nov 28;278(5343):1638-41.
Science (New York, N.Y.)
Chow, Chi-Wing; Rincon, Mercedes; Cavanagh, Julie; Dickens, Martin; and Davis, Roger J., "Nuclear accumulation of NFAT4 opposed by the JNK signal transduction pathway" (1997). Open Access Articles. 1645.