HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 281, Issue 16, 11405-11412, April 21, 2006

This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: 281/16/11405    most recent M600477200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Wesche, J. Articles by Olsnes, S. Search for Related Content PubMed PubMed Citation Articles by Wesche, J. Articles by Olsnes, S. Social Bookmarking                      What's this?

FGF-1 and FGF-2 Require the Cytosolic Chaperone Hsp90 for Translocation into the Cytosol and the Cell Nucleus^*

Jørgen Wesche¹, Jdrzej Maecki², Antoni Widocha, Camilla Skiple Skjerpen, Peter Claus, and Sjur Olsnes

From the Institute for Cancer Research at the Norwegian Radium Hospital, University of Oslo, Montebello, 0310 Oslo, Norway and the Department of Neuroanatomy, Hannover Medical School, D-30625 Hannover, Germany

Similarly to many protein toxins, the growth factors fibroblast growth factor 1 (FGF-1) and FGF-2 translocate from endosomes into the cytosol. It was recently found that certain toxins are dependent on cytosolic Hsp90 for efficient translocation across the endosomal membrane. We therefore investigated the requirement for Hsp90 in FGF translocation. We found that low concentrations of the specific Hsp90 inhibitors, geldanamycin and radicicol, completely blocked the translocation of FGF-1 and FGF-2 to the cytosol and the nucleus. The drugs did not interfere with the initial binding of FGF-1 to the growth factor receptors at the cell-surface or with the subsequent internalization of the growth factors into endosomes. The activation of known signaling cascades downstream of the growth factor receptors was also not affected by the drugs. The data indicate that the drugs block translocation from endosomes to the cytosol implying that Hsp90 is required for translocation of FGF-1 and FGF-2 across the endosomal membrane.

Received for publication, January 17, 2006 , and in revised form, February 22, 2006.

^* This work was supported by the Norwegian Cancer Society, the Novo Nordisk Foundation, the Norwegian Research Council, Blix Fund for the Promotion of Medical Research, Rachel and Otto Kr. Bruun's legat, Ragnar Mørk's legat, Torsteds legat, and by the Jahre Foundation. 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.

² Present address: Inst. of Medical Biochemistry, Medical College Jagiellonian University, 31-034 Krakow, Poland.

¹ To whom correspondence should be addressed. Tel.: 47-22-93-42-93; Fax: 47-22-50-86-92; E-mail: jorgen.wesche{at}labmed.uio.no.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				V. Stepanova, T. Lebedeva, A. Kuo, S. Yarovoi, S. Tkachuk, S. Zaitsev, K. Bdeir, I. Dumler, M. S. Marks, Y. Parfyonova, et al. Nuclear translocation of urokinase-type plasminogen activator Blood, July 1, 2008; 112(1): 100 - 110. [Abstract] [Full Text] [PDF]

				V. Sorensen, Y. Zhen, M. Zakrzewska, E. M. Haugsten, S. Walchli, T. Nilsen, S. Olsnes, and A. Wiedlocha Phosphorylation of Fibroblast Growth Factor (FGF) Receptor 1 at Ser777 by p38 Mitogen-Activated Protein Kinase Regulates Translocation of Exogenous FGF1 to the Cytosol and Nucleus Mol. Cell. Biol., June 15, 2008; 28(12): 4129 - 4141. [Abstract] [Full Text] [PDF]

				J Buratini Jr., M.G.L Pinto, A.C Castilho, R.L Amorim, I.C Giometti, V.M Portela, E.S Nicola, and C.A Price Expression and Function of Fibroblast Growth Factor 10 and Its Receptor, Fibroblast Growth Factor Receptor 2B, in Bovine Follicles Biol Reprod, October 1, 2007; 77(4): 743 - 750. [Abstract] [Full Text] [PDF]

				H. Zheng, J. Shi, X. Fang, Y. Li, S. Vang, W. Fan, J. Wang, Z. Zhang, W. Wang, K. Kristiansen, et al. FGF: A web tool for Fishing Gene Family in a whole genome database Nucleic Acids Res., July 13, 2007; 35(suppl_2): W121 - W125. [Abstract] [Full Text] [PDF]

				V. Sorensen, A. Wiedlocha, E. M. Haugsten, D. Khnykin, J. Wesche, and S. Olsnes Different abilities of the four FGFRs to mediate FGF-1 translocation are linked to differences in the receptor C-terminal tail J. Cell Sci., October 15, 2006; 119(20): 4332 - 4341. [Abstract] [Full Text] [PDF]