Nuclear export of NF-ATc enhanced by glycogen synthase kinase-3.

Science (New York, N.Y.) ·Vol. 275 ·No. 5308 ·1997-03-28 ·Pages 1930-4

Beals CR, Sheridan CM, Turck CW, Gardner P, Crabtree GR

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,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,metabolism Transfection

Chemicals

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

Authors & Affiliations

5 authors, click to expand affiliations / ORCID

Beals C R

Howard Hughes Medical Institute, Department of Developmental Biology, Stanford University, Stanford, CA 94305, USA.

Sheridan C M

Turck C W

Gardner P

Crabtree G R

Article Info

Journal

Science (New York, N.Y.)

Abbr.

Science

ISSN

0036-8075

DOI

10.1126/science.275.5308.1930

Published

1997-03-28

Pages

1930-4

Language

English

Region

United States

NLM ID

0404511

Subset

External Links

PubMed source DOI: 10.1126/science.275.5308.1930 View journal details

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Nuclear export of NF-ATc enhanced by glycogen synthase kinase-3.

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