Abstract
The transcription factor NF-AT responds to Ca2+-calcineurin signals by translocating to the nucleus, where it participates in the activation of early immune response genes. Calcineurin dephosphorylates conserved serine residues in the amino terminus of NF-AT, resulting in nuclear import. Purification of the NF-AT kinase revealed that it is composed of a priming kinase activity and glycogen synthase kinase-3 (GSK-3). GSK-3 phosphorylates conserved serines necessary for nuclear export, promotes nuclear exit, and thereby opposes Ca2+-calcineurin signaling. Because GSK-3 responds to signals initiated by Wnt and other ligands, NF-AT family members could be effectors of these pathways.
MeSH terms
-
Amino Acid Sequence
-
Animals
-
Biological Transport
-
Brain / enzymology
-
COS Cells
-
Calcineurin
-
Calcium / metabolism
-
Calcium-Calmodulin-Dependent Protein Kinases / metabolism*
-
Calmodulin-Binding Proteins / metabolism
-
Cell Nucleus / metabolism*
-
Cloning, Molecular
-
Cyclic AMP-Dependent Protein Kinases / metabolism
-
DNA-Binding Proteins / genetics
-
DNA-Binding Proteins / metabolism*
-
Glycogen Synthase Kinase 3
-
Glycogen Synthase Kinases
-
Humans
-
Molecular Sequence Data
-
NFATC Transcription Factors
-
Nuclear Proteins*
-
Phosphoprotein Phosphatases / metabolism
-
Phosphorylation
-
Rats
-
Recombinant Fusion Proteins / metabolism
-
Signal Transduction
-
Transcription Factors / genetics
-
Transcription Factors / metabolism*
-
Transfection
Substances
-
Calmodulin-Binding Proteins
-
DNA-Binding Proteins
-
NFATC Transcription Factors
-
NFATC1 protein, human
-
Nuclear Proteins
-
Recombinant Fusion Proteins
-
Transcription Factors
-
Glycogen Synthase Kinases
-
Cyclic AMP-Dependent Protein Kinases
-
Calcium-Calmodulin-Dependent Protein Kinases
-
Glycogen Synthase Kinase 3
-
Calcineurin
-
Phosphoprotein Phosphatases
-
Calcium