Molecular Biology of the Cell click for CBE Life Science Education Page

Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
QUICK SEARCH:   [advanced]


     

Originally published as MBC in Press, 10.1091/mbc.E04-05-0389 on December 1, 2004

Vol. 16, Issue 2, 794-810, February 2005

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
E04-05-0389v1
16/2/794    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Wiedlocha, A.
Right arrow Articles by Olsnes, S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Wiedlocha, A.
Right arrow Articles by Olsnes, S.

Phosphorylation-regulated Nucleocytoplasmic Trafficking of Internalized Fibroblast Growth Factor-1

Antoni Wiedlocha *, Trine Nilsen, Jørgen Wesche, Vigdis Sørensen, Jedrzej Malecki, Ewa Marcinkowska, and Sjur Olsnes

Institute for Cancer Research, The Norwegian Radium Hospital, 0310 Oslo, Norway

Submitted May 12, 2004; Revised November 4, 2004; Accepted November 17, 2004
Monitoring Editor: Carl-Henrik Heldin

Fibroblast growth factor-1 (FGF-1), which stimulates cell growth, differentiation, and migration, is capable of crossing cellular membranes to reach the cytosol and the nucleus in cells containing specific FGF receptors. The cell entry process can be monitored by phosphorylation of the translocated FGF-1. We present evidence that phosphorylation of FGF-1 occurs in the nucleus by protein kinase C (PKC){delta}. The phosphorylated FGF-1 is subsequently exported to the cytosol. A mutant growth factor where serine at the phosphorylation site is exchanged with glutamic acid, to mimic phosphorylated FGF-1, is constitutively transported to the cytosol, whereas a mutant containing alanine at this site remains in the nucleus. The export can be blocked by leptomycin B, indicating active and receptor-mediated nuclear export of FGF-1. Thapsigargin, but not leptomycin B, prevents the appearance of active PKC{delta} in the nucleus, and FGF-1 is in this case phosphorylated in the cytosol. Leptomycin B increases the amount of phosphorylated FGF-1 in the cells by preventing dephosphorylation of the growth factor, which seems to occur more rapidly in the cytoplasm than in the nucleus. The nucleocytoplasmic trafficking of the phosphorylated growth factor is likely to play a role in the activity of internalized FGF-1.

Article published online ahead of print in MBC in Press on December 1, 2004 (http://www.molbiolcell.org/cgi/doi/10.1091/mbc.E04-05-0389).

* Corresponding author. E-mail address: antoni.wiedlocha{at}labmed.uio.no.




This article has been cited by other articles:


Home page
 J. Biol. Chem.Home page
M. Zakrzewska, A. Wiedlocha, A. Szlachcic, D. Krowarsch, J. Otlewski, and S. Olsnes
Increased Protein Stability of FGF1 Can Compensate for Its Reduced Affinity for Heparin
J. Biol. Chem., September 11, 2009; 284(37): 25388 - 25403.
[Abstract] [Full Text] [PDF]

Home page
 Infect. Immun.Home page
K. Heine, S. Pust, S. Enzenmuller, and H. Barth
ADP-Ribosylation of Actin by the Clostridium botulinum C2 Toxin in Mammalian Cells Results in Delayed Caspase-Dependent Apoptotic Cell Death
Infect. Immun., October 1, 2008; 76(10): 4600 - 4608.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
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]

Home page
 J. Biol. Chem.Home page
T. Nilsen, K. R. Rosendal, V. Sorensen, J. Wesche, S. Olsnes, and A. Wiedlocha
A Nuclear Export Sequence Located on a beta-Strand in Fibroblast Growth Factor-1
J. Biol. Chem., September 7, 2007; 282(36): 26245 - 26256.
[Abstract] [Full Text] [PDF]

Home page
 J. Cell Sci.Home page
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]

Home page
 Am. J. Physiol. Gastrointest. Liver Physiol.Home page
M. Le, L. Krilov, J. Meng, K. Chapin-Kennedy, S. Ceryak, and B. Bouscarel
Bile acids stimulate PKC{alpha} autophosphorylation and activation: role in the attenuation of prostaglandin E1-induced cAMP production in human dermal fibroblasts
Am J Physiol Gastrointest Liver Physiol, August 1, 2006; 291(2): G275 - G287.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
J. Wesche, J. Malecki, A. Wiedlocha, C. S. Skjerpen, P. Claus, and S. Olsnes
FGF-1 and FGF-2 Require the Cytosolic Chaperone Hsp90 for Translocation into the Cytosol and the Cell Nucleus
J. Biol. Chem., April 21, 2006; 281(16): 11405 - 11412.
[Abstract] [Full Text] [PDF]


Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
Copyright © 2005 by The American Society for Cell Biology. Terms of copyright protection, warranties, and disclaimers.