ROLE OF KINASES AND THE PHOSPHATASE CALCINEURIN IN THE NUCLEAR SHUTTLING OF TRANSCRIPTION FACTOR NF-AT4

A NEW facet of calcium signallin involves the nuclear import of the NF -AT transcription factors from their dormant position in the cytoplasm (1-3). The protein phosphatase calcineurin appears to play an essentia l role in activating NF-AT nuclear import, as the calcineurin inhibito rs cyclosporin A and FK506 block dephosphorylation and nuclear import of NF-AT (refs 4-7). Here we show that calcium signalling induces an a ssociation between NF-AT4 and calcineurin, and that these molecules ar e transported, as a complex, to the nucleus, where calcineurin continu es to dephosphorylate NF-AT4. We propose that a nuclear complex of NF- AT4 and calcineurin maintains calcium signalling by counteracting a vi gorous nuclear NF-AT kinase.