Role of kinases and the phosphatase calcineurin in the nuclear shuttling of transcription factor NF-AT4

Nature. 1996 Jul 25;382(6589):370-3. doi: 10.1038/382370a0.


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


  • Calmodulin-Binding Proteins
  • DNA-Binding Proteins
  • NFATC Transcription Factors
  • Nuclear Proteins
  • Protein Sorting Signals
  • Transcription Factors
  • DNA
  • Protein Kinases
  • Calcineurin
  • Phosphoprotein Phosphatases
  • Calcium