Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.
Subscribe

Logo for

Mol. Cell. Biol. 20 (19): 7273-7281

Copyright © 2000 by the American Society for Microbiology. All rights reserved.

Molecular and Cellular Biology, October 2000, p. 7273-7281, Vol. 20, No. 19
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Regulation of STAT1 Nuclear Export by Jak1

Kerri Mowen and Michael David*

Department of Biology, University of California at San Diego, La Jolla, California 92093

Received 23 May 2000/Returned for modification 20 June 2000/Accepted 27 June 2000

Signal transducer and activator of transcription 1 (STAT1) mediates gene expression in response to cytokines and growth factors. Activation of STAT1 is achieved through its tyrosine phosphorylation, a process that involves Jak tyrosine kinases. Here we show that STAT1, although phosphorylated on Y701, is unable to localize in the nucleus in the absence of Jak1 or Jak1 kinase activity. In contrast, the nuclear accumulation of STAT1 in Tyk2-deficient cells remains intact. Nuclear presence of tyrosine-phosphorylated STAT1 could be restored in Jak1-deficient cells by leptomycin B, an inhibitor of nuclear export. Amino acids 197 to 205 of STAT1 were found to encode a leucine-rich nuclear export signal (NES). An Lright-arrowA mutation within the NES restored nuclear retention of STAT1 in Jak1-deficient cells. Impaired binding of the transcriptional coactivator CBP to tyrosine-phosphorylated STAT1 derived from Jak1-deficient cells offers a model for the intermolecular regulation of the nuclear export sequence.

* Corresponding author. Mailing address: University of California, San Diego, Department of Biology, Bonner Hall 3138, 9500 Gilman Drive, La Jolla, CA 92093-0322. Phone: (858) 822-1108. Fax: (858) 822-1106. E-mail:midavid{at}ucsd.edu.

Molecular and Cellular Biology, October 2000, p. 7273-7281, Vol. 20, No. 19
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Inhibitor of {kappa}B Kinase {epsilon} (IKK{epsilon}), STAT1, and IFIT2 Proteins Define Novel Innate Immune Effector Pathway against West Nile Virus Infection.
O. Perwitasari, H. Cho, M. S. Diamond, and M. Gale Jr. (2011)
J. Biol. Chem. 286, 44412-44423
   Abstract »    Full Text »    PDF »
Signal Transducer and Activator of Transcription 1 Regulates Both Cytotoxic and Prosurvival Functions in Tumor Cells.
N. N. Khodarev, A. J. Minn, E. V. Efimova, T. E. Darga, E. Labay, M. Beckett, H. J. Mauceri, B. Roizman, and R. R. Weichselbaum (2007)
Cancer Res. 67, 9214-9220
   Abstract »    Full Text »    PDF »
Phosphorylation of Both Nucleoplasmin Domains Is Required for Activation of Its Chromatin Decondensation Activity.
S. Banuelos, M. J. Omaetxebarria, I. Ramos, M. R. Larsen, I. Arregi, O. N. Jensen, J. M. Arizmendi, A. Prado, and A. Muga (2007)
J. Biol. Chem. 282, 21213-21221
   Abstract »    Full Text »    PDF »
The structure of nucleosome assembly protein 1.
Y.-J. Park and K. Luger (2006)
PNAS 103, 1248-1253
   Abstract »    Full Text »    PDF »
Modification of the Stat1 SH2 Domain Broadly Improves Interferon Efficacy in Proportion to p300/CREB-binding Protein Coactivator Recruitment.
Y. Zhang, K. Takami, M. S. Lo, G. Huang, Q. Yu, W. T. Roswit, and M. J. Holtzman (2005)
J. Biol. Chem. 280, 34306-34315
   Abstract »    Full Text »    PDF »
Domain 2 of the Urokinase Receptor Contains an Integrin-interacting Epitope with Intrinsic Signaling Activity: GENERATION OF A NEW INTEGRIN INHIBITOR.
B. Degryse, M. Resnati, R.-P. Czekay, D. J. Loskutoff, and F. Blasi (2005)
J. Biol. Chem. 280, 24792-24803
   Abstract »    Full Text »    PDF »
The Second Open Reading Frame of the Avian Reovirus S1 Gene Encodes a Transcription-Dependent and CRM1-Independent Nucleocytoplasmic Shuttling Protein.
C. Costas, J. Martinez-Costas, G. Bodelon, and J. Benavente (2005)
J. Virol. 79, 2141-2150
   Abstract »    Full Text »    PDF »
Identification of MoKA, a Novel F-Box Protein That Modulates Kruppel-Like Transcription Factor 7 Activity.
S. Smaldone, F. Laub, C. Else, C. Dragomir, and F. Ramirez (2004)
Mol. Cell. Biol. 24, 1058-1069
   Abstract »    Full Text »    PDF »
Interferon-{gamma}: an overview of signals, mechanisms and functions.
K. Schroder, P. J. Hertzog, T. Ravasi, and D. A. Hume (2004)
J. Leukoc. Biol. 75, 163-189
   Abstract »    Full Text »    PDF »
DNA Binding Activity of Cytoplasmic Phosphorylated Stat6 Is Masked by an Interaction with a Detergent-sensitive Factor.
M. O. Daines, R. P. Andrews, W. Chen, S. A. El-Zayaty, and G. K. K. Hershey (2003)
J. Biol. Chem. 278, 30971-30974
   Abstract »    Full Text »    PDF »
The Ins and Outs of STAT1 Nuclear Transport.
K. M. McBride and N. C. Reich (2003)
Sci. STKE 2003, re13
   Abstract »    Full Text »    PDF »
The Epstein-Barr Virus SM Protein Induces STAT1 and Interferon-Stimulated Gene Expression.
V. Ruvolo, L. Navarro, C. E. Sample, M. David, S. Sung, and S. Swaminathan (2003)
J. Virol. 77, 3690-3701
   Abstract »    Full Text »    PDF »
Nipah Virus V Protein Evades Alpha and Gamma Interferons by Preventing STAT1 and STAT2 Activation and Nuclear Accumulation.
J. J. Rodriguez, J.-P. Parisien, and C. M. Horvath (2002)
J. Virol. 76, 11476-11483
   Abstract »    Full Text »    PDF »
Analysis of the Life Cycle of Stat6. CONTINUOUS CYCLING OF STAT6 IS REQUIRED FOR IL-4 SIGNALING.
R. P. Andrews, M. B. Ericksen, C. M. Cunningham, M. O. Daines, and G. K. K. Hershey (2002)
J. Biol. Chem. 277, 36563-36569
   Abstract »    Full Text »    PDF »
The Coiled Coil Region (Amino Acids 129-250) of the Tumor Suppressor Protein Adenomatous Polyposis Coli (APC). ITS STRUCTURE AND ITS INTERACTION WITH CHROMOSOME MAINTENANCE REGION 1 (Crm-1).
L. Tickenbrock, J. Cramer, I. R. Vetter, and O. Muller (2002)
J. Biol. Chem. 277, 32332-32338
   Abstract »    Full Text »    PDF »
A nuclear export signal within the high mobility group domain regulates the nucleocytoplasmic translocation of SOX9 during sexual determination.
S. Gasca, J. Canizares, P. de Santa Barbara, C. Mejean, F. Poulat, P. Berta, and B. Boizet-Bonhoure (2002)
PNAS 99, 11199-11204
   Abstract »    Full Text »    PDF »
Selective STAT Protein Degradation Induced by Paramyxoviruses Requires both STAT1 and STAT2 but Is Independent of Alpha/Beta Interferon Signal Transduction.
J.-P. Parisien, J. F. Lau, J. J. Rodriguez, C. M. Ulane, and C. M. Horvath (2002)
J. Virol. 76, 4190-4198
   Abstract »    Full Text »    PDF »
Nuclear Export of Mammalian PERIOD Proteins.
E. L. Vielhaber, D. Duricka, K. S. Ullman, and D. M. Virshup (2001)
J. Biol. Chem. 276, 45921-45927
   Abstract »    Full Text »    PDF »
Regulated nuclear export of the homeodomain transcription factor Prospero.
Z Demidenko, P Badenhorst, T Jones, X Bi, and M. Mortin (2001)
Development 128, 1359-1367
   Abstract »    PDF »
The Receptor Interaction Region of Tyk2 Contains a Motif Required for Its Nuclear Localization.
J. Ragimbeau, E. Dondi, A. Vasserot, P. Romero, G. Uze, and S. Pellegrini (2001)
J. Biol. Chem. 276, 30812-30818
   Abstract »    Full Text »    PDF »

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882