The nuclear factor of activated T cells (NFAT) group of transcription
factors is retained in the cytoplasm of quiescent cells, NFAT activati
on is mediated in part, by induced nuclear import, This process requir
es calcium-dependent dephosphorylation of NFAT caused by the phosphata
se calcineurin, The c-Jun amino-terminal kinase (JNK) phosphorylates N
FAT4 on two sites, Mutational removal of the JNK phosphorylation sites
caused constitutive nuclear localization of NFAT4, in contrast, JNK a
ctivation in calcineurin-stimulated cells caused nuclear exclusion of
NFAT4. These findings show that the nuclear accumulation of NFAT4 prom
oted by calcineurin is opposed by the JNK signal transduction pathway.