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Science 28 March 1997:
Vol. 275. no. 5308, pp. 1930 - 1933
DOI: 10.1126/science.275.5308.1930
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Reports

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

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.

C. R. Beals and G. R. Crabtree, Howard Hughes Medical Institute, Department of Developmental Biology, Stanford University, Stanford, CA 94305, USA.
C. M. Sheridan and P. Gardner, Department of Molecular Pharmacology, Stanford University, Stanford, CA 94305, USA.
C. W. Turck, Howard Hughes Medical Institute, University of California, San Francisco, CA 94143, USA.

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Wnt Target Genes Identified by DNA Microarrays in Immature CD34+ Thymocytes Regulate Proliferation and Cell Adhesion.
F. J. T. Staal, F. Weerkamp, M. R. M. Baert, C. M. M. van den Burg, M. van Noort, E. F. E. de Haas, and J. J. M. van Dongen (2004)
J. Immunol. 172, 1099-1108
   Abstract »    Full Text »    PDF »
GSK-3 kinases enhance calcineurin signaling by phosphorylation of RCNs.
Z. Hilioti, D. A. Gallagher, S. T. Low-Nam, P. Ramaswamy, P. Gajer, T. J. Kingsbury, C. J. Birchwood, A. Levchenko, and K. W. Cunningham (2004)
Genes & Dev. 18, 35-47
   Abstract »    Full Text »    PDF »
Ras, Akt, and Mechanotransduction in the Cardiac Myocyte.
P. H. Sugden (2003)
Circ. Res. 93, 1179-1192
   Abstract »    Full Text »    PDF »
Control of Cardiac Growth and Function by Calcineurin Signaling.
R. B. Vega, R. Bassel-Duby, and E. N. Olson (2003)
J. Biol. Chem. 278, 36981-36984
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Nuclear Factor of Activated T Cells c Is a Target of p38 Mitogen-Activated Protein Kinase in T Cells.
C.-C. Wu, S.-C. Hsu, H.-m. Shih, and M.-Z. Lai (2003)
Mol. Cell. Biol. 23, 6442-6454
   Abstract »    Full Text »    PDF »
Transcriptional regulation by calcium, calcineurin, and NFAT.
P. G. Hogan, L. Chen, J. Nardone, and A. Rao (2003)
Genes & Dev. 17, 2205-2232
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A SOX9 Defect of Calmodulin-dependent Nuclear Import in Campomelic Dysplasia/Autosomal Sex Reversal.
A. Argentaro, H. Sim, S. Kelly, S. Preiss, A. Clayton, D. A. Jans, and V. R. Harley (2003)
J. Biol. Chem. 278, 33839-33847
   Abstract »    Full Text »    PDF »
Constitutively Active Protein Kinase B Enhances Lck and Erk Activities and Influences Thymocyte Selection and Activation.
S.-Y. Na, A. Patra, Y. Scheuring, A. Marx, M. Tolaini, D. Kioussis, B. Hemmings, T. Hunig, and U. Bommhardt (2003)
J. Immunol. 171, 1285-1296
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Constitutively Active Glycogen Synthase Kinase-3{beta} Gene Transfer Sustains Apoptosis, Inhibits Proliferation of Vascular Smooth Muscle Cells, and Reduces Neointima Formation After Balloon Injury in Rats.
K.-W. Park, H.-M. Yang, S.-W. Youn, H.-J. Yang, I.-H. Chae, B.-H. Oh, M.-M. Lee, Y.-B. Park, Y.-S. Choi, H.-S. Kim, et al. (2003)
Arterioscler Thromb Vasc Biol 23, 1364-1369
   Abstract »    Full Text »    PDF »
Protein kinase A phosphorylation modulates transport of the polypyrimidine tract-binding protein.
J. Xie, J.-A. Lee, T. L. Kress, K. L. Mowry, and D. L. Black (2003)
PNAS 100, 8776-8781
   Abstract »    Full Text »    PDF »
Nuclear Factor of Activated T Cells 2 Transactivation in Mast Cells: A NOVEL ISOFORM-SPECIFIC TRANSACTIVATION DOMAIN CONFERS UNIQUE Fc{epsilon}RI RESPONSIVENESS.
M. B. Hock and M. A. Brown (2003)
J. Biol. Chem. 278, 26695-26703
   Abstract »    Full Text »    PDF »
Glycogen Synthase Kinase 3{beta}-Mediated Apoptosis of Primary Cortical Astrocytes Involves Inhibition of Nuclear Factor {kappa}B Signaling.
J. F. Sanchez, L. F. Sniderhan, A. L. Williamson, S. Fan, S. Chakraborty-Sett, and S. B. Maggirwar (2003)
Mol. Cell. Biol. 23, 4649-4662
   Abstract »    Full Text »    PDF »
Transforming Growth Factor {beta} Blocks Tec Kinase Phosphorylation, Ca2+ Influx, and NFATc Translocation Causing Inhibition of T Cell Differentiation.
C.-H. Chen, C. Seguin-Devaux, N. A. Burke, T. B. Oriss, S. C. Watkins, N. Clipstone, and A. Ray (2003)
J. Exp. Med. 197, 1689-1699
   Abstract »    Full Text »    PDF »
Human Herpesvirus 8-Encoded vGPCR Activates Nuclear Factor of Activated T Cells and Collaborates with Human Immunodeficiency Virus Type 1 Tat.
S. Pati, J. S. Foulke Jr., O. Barabitskaya, J. Kim, B. C. Nair, D. Hone, J. Smart, R. A. Feldman, and M. Reitz (2003)
J. Virol. 77, 5759-5773
   Abstract »    Full Text »    PDF »
A Constitutively Active NFATc1 Mutant Induces a Transformed Phenotype in 3T3-L1 Fibroblasts.
J. W. Neal and N. A. Clipstone (2003)
J. Biol. Chem. 278, 17246-17254
   Abstract »    Full Text »    PDF »
GSK-3: tricks of the trade for a multi-tasking kinase.
B. W. Doble and J. R. Woodgett (2003)
J. Cell Sci. 116, 1175-1186
   Abstract »    Full Text »    PDF »
Dictyostelium Differentiation-inducing Factor-3 Activates Glycogen Synthase Kinase-3beta and Degrades Cyclin D1 in Mammalian Cells.
F. Takahashi-Yanaga, Y. Taba, Y. Miwa, Y. Kubohara, Y. Watanabe, M. Hirata, S. Morimoto, and T. Sasaguri (2003)
J. Biol. Chem. 278, 9663-9670
   Abstract »    Full Text »    PDF »
Protein Kinase A Negatively Modulates the Nuclear Accumulation of NF-ATc1 by Priming for Subsequent Phosphorylation by Glycogen Synthase Kinase-3.
C. M. Sheridan, E. K. Heist, C. R. Beals, G. R. Crabtree, and P. Gardner (2002)
J. Biol. Chem. 277, 48664-48676
   Abstract »    Full Text »    PDF »
Commitment of Activated T Cells to Secondary Responsiveness Is Enhanced by Signals Mediated by cAMP-Dependent Protein Kinase A-I.
M. Vig, A. George, R. Sen, J. Durdik, S. Rath, and V. Bal (2002)
Mol. Pharmacol. 62, 1471-1481
   Abstract »    Full Text »    PDF »
The Regulation of Glycogen Synthase Kinase-3 Nuclear Export by Frat/GBP.
J. Franca-Koh, M. Yeo, E. Fraser, N. Young, and T. C. Dale (2002)
J. Biol. Chem. 277, 43844-43848
   Abstract »    Full Text »    PDF »


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