Abstract
A new facet of calcium signalling involves the nuclear import of the NF-AT transcription factors from their dormant position in the cytoplasm. The protein phosphatase calcineurin appears to play an essential role in activating NF-AT nuclear import, as the calcineurin inhibitors cyclosporin A and FK506 block dephosphorylation and nuclear import of NF-AT (refs 4-7). Here we show that calcium signalling induces an association between NF-AT4 and calcineurin, and that these molecules are transported, as a complex, to the nucleus, where calcineurin continues to dephosphorylate NF-AT4. We propose that a nuclear complex of NF-AT4 and calcineurin maintains calcium signalling by counteracting a vigorous nuclear NF-AT kinase.
Publication types
-
Research Support, Non-U.S. Gov't
-
Research Support, U.S. Gov't, P.H.S.
MeSH terms
-
Amino Acid Sequence
-
Animals
-
Base Sequence
-
Calcineurin
-
Calcium / metabolism
-
Calmodulin-Binding Proteins / genetics
-
Calmodulin-Binding Proteins / metabolism*
-
Cell Line
-
Cell Nucleus / metabolism*
-
Cricetinae
-
DNA
-
DNA-Binding Proteins / metabolism*
-
Enzyme Activation
-
Humans
-
Molecular Sequence Data
-
Mutagenesis
-
NFATC Transcription Factors
-
Nuclear Proteins*
-
Phosphoprotein Phosphatases / genetics
-
Phosphoprotein Phosphatases / metabolism*
-
Phosphorylation
-
Protein Kinases / metabolism*
-
Protein Sorting Signals / metabolism
-
Transcription Factors / metabolism*
-
Tumor Cells, Cultured
Substances
-
Calmodulin-Binding Proteins
-
DNA-Binding Proteins
-
NFATC Transcription Factors
-
Nuclear Proteins
-
Protein Sorting Signals
-
Transcription Factors
-
DNA
-
Protein Kinases
-
Calcineurin
-
Phosphoprotein Phosphatases
-
Calcium