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.
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Citation: 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.