Nuclear Export of NF-ATc Enhanced by Glycogen Synthase Kinase-3

Chan R. Beals, Colleen M. Sheridan, Christoph W. Turck, Phyllis Gardner, Gerald R. Crabtree

doi:10.1126/science.275.5308.1930

Nuclear Export of NF-ATc Enhanced by Glycogen Synthase Kinase-3

DOI Web Site 被引用文献14件

Chan R. Beals

C. R. Beals and G. R. Crabtree, Howard Hughes Medical Institute, Department of Developmental Biology, Stanford University, Stanford, CA 94305, USA.
Colleen M. Sheridan

C. M. Sheridan and P. Gardner, Department of Molecular Pharmacology, Stanford University, Stanford, CA 94305, USA.
Christoph W. Turck

C. W. Turck, Howard Hughes Medical Institute, University of California, San Francisco, CA 94143, USA.
Phyllis Gardner

C. M. Sheridan and P. Gardner, Department of Molecular Pharmacology, Stanford University, Stanford, CA 94305, USA.
Gerald R. Crabtree

C. R. Beals and G. R. Crabtree, Howard Hughes Medical Institute, Department of Developmental Biology, Stanford University, Stanford, CA 94305, USA.

抄録

<jats:p> The transcription factor NF-AT responds to Ca <jats:sup>2+</jats:sup> -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 Ca <jats:sup>2+</jats:sup> -calcineurin signaling. Because GSK-3 responds to signals initiated by Wnt and other ligands, NF-AT family members could be effectors of these pathways. </jats:p>