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

J. Biol. Chem. 280 (2): 1123-1131

© 2005 by The American Society for Biochemistry and Molecular Biology, Inc.

STAT5B-mediated Growth Hormone Signaling Is Organized by Highly Dynamic Microtubules in Hepatic Cells*

Thu Phung-Koskas{ddagger}, Antoine Pilon{ddagger}, Christian Poüs{ddagger}, Cécile Betzina{ddagger}, Marie Sturm{ddagger}, Marie-Lise Bourguet-Kondracki§, Geneviève Durand{ddagger}, , and Anne Drechou{ddagger}

{ddagger}Laboratoire de Biochimie et de Biologie Cellulaire, EA 1595, Faculté de Pharmacie, 5, rue JB. Clément, 92296 Chatenay-Malabry Cedex, France and the §Laboratoire de Chimie, CNRS UMR 5154, Muséum National Histoire Naturelle, 63 rue Buffon, 75005 Paris, France

Abstract: In the last decade, the notion that microtubules are critical to the spatial organization of signal transduction and contribute to the transmission of signals to downstream targets has been proposed. Because the STAT5B transduction and transcription factor is the major STAT protein activated by growth hormone stimulation in hepatocytes and is a crossroads between many signaling pathways, we studied the involvement of microtubules in STAT5B-mediated growth hormone signaling pathway in the highly differentiated and polarized WIF-B hepatic cell line. We showed that depolymerization of the microtubule network impaired STAT5B translocation to the nucleus upon growth hormone treatment. A significant amount of STAT5B binds to microtubules, while STAT5A and STAT3 are exclusively compartmentalized in the cytosol. Moreover, taxol-induced stabilization of microtubules released STAT5B from its binding, and we show that STAT5B binds specifically to the highly dynamic microtubules and is absent of the stable microtubule subpopulation. The specific involvement of dynamic microtubule subpopulation in growth hormone signaling pathway was confirmed by the inhibition of growth hormone-induced STAT5B nuclear translocation after stabilization of microtubules or specific disruption of highly dynamic microtubules. Upon growth hormone treatment, MT-bound STAT5B was rapidly released from microtubules by a dynein-dependent transport to the nucleus. Altogether, our findings indicate that the labile microtubule subpopulation specifically and dynamically organizes STAT5B-mediated growth hormone signaling in hepatic cells.

Received for publication August 30, 2004. Revision received October 12, 2004.

* This work was supported by a grant from the Institut de Recherches Internationales Servier. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

To whom correspondence should be addressed. Tel.: 33-1-46-83-54-78; Fax: 33-1-46-83-58-02; E-mail: anne.drechou{at}cep.u-psud.fr.

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Membrane Microdomains and Cytoskeleton Organization Shape and Regulate the IL-7 Receptor Signalosome in Human CD4 T-cells.
B. Tamarit, F. Bugault, A.-H. Pillet, V. Lavergne, P. Bochet, N. Garin, U. Schwarz, J. Theze, and T. Rose (2013)
J. Biol. Chem. 288, 8691-8701
   Abstract »    Full Text »    PDF »
Hepatic microtubule acetylation and stability induced by chronic alcohol exposure impair nuclear translocation of STAT3 and STAT5B, but not Smad2/3.
D. J. Fernandez, D. J. Tuma, and P. L. Tuma (2012)
Am J Physiol Gastrointest Liver Physiol 303, G1402-G1415
   Abstract »    Full Text »    PDF »
Mechanism of Microtubule-facilitated "Fast Track" Nuclear Import.
D. M. Roth, G. W. Moseley, C. W. Pouton, and D. A. Jans (2011)
J. Biol. Chem. 286, 14335-14351
   Abstract »    Full Text »    PDF »
Starvation-induced Hyperacetylation of Tubulin Is Required for the Stimulation of Autophagy by Nutrient Deprivation.
C. Geeraert, A. Ratier, S. G. Pfisterer, D. Perdiz, I. Cantaloube, A. Rouault, S. Pattingre, T. Proikas-Cezanne, P. Codogno, and C. Pous (2010)
J. Biol. Chem. 285, 24184-24194
   Abstract »    Full Text »    PDF »
Kinesin-1 Regulates Microtubule Dynamics via a c-Jun N-terminal Kinase-dependent Mechanism.
V. Daire, J. Giustiniani, I. Leroy-Gori, M. Quesnoit, S. Drevensek, A. Dimitrov, F. Perez, and C. Pous (2009)
J. Biol. Chem. 284, 31992-32001
   Abstract »    Full Text »    PDF »
In vivo identification of novel STAT5 target genes.
B. Basham, M. Sathe, J. Grein, T. McClanahan, A. D'Andrea, E. Lees, and A. Rascle (2008)
Nucleic Acids Res. 36, 3802-3818
   Abstract »    Full Text »    PDF »
Constitutive nuclear import of latent and activated STAT5a by its coiled coil domain.
J. Iyer and N. C. Reich (2008)
FASEB J 22, 391-400
   Abstract »    Full Text »    PDF »
Requirement for the Dynein Light Chain km23-1 in a Smad2-dependent Transforming Growth Factor-beta Signaling Pathway.
Q. Jin, W. Ding, and K. M. Mulder (2007)
J. Biol. Chem. 282, 19122-19132
   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