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

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 investigat...

Full description

Saved in:
Bibliographic Details
Published in:The Journal of biological chemistry 2006-04, Vol.281 (16), p.11405-11412
Main Authors: Wesche, Jørgen, Małecki, Jędrzej, Więdłocha, Antoni, Skjerpen, Camilla Skiple, Claus, Peter, Olsnes, Sjur
Format: Article
Language:English
Subjects:
Animals
Benzoquinones
Cell Line
Cell Nucleus - metabolism
Cell Proliferation
Cytosol - metabolism
Dose-Response Relationship, Drug
Electrophoresis, Polyacrylamide Gel
Endosomes - metabolism
Fibroblast Growth Factor 1 - metabolism
Fibroblast Growth Factor 1 - physiology
Fibroblast Growth Factor 2 - metabolism
Fibroblast Growth Factor 2 - physiology
Heparin - pharmacology
HSP90 Heat-Shock Proteins - metabolism
Humans
Lactams, Macrocyclic
Lactones - pharmacology
Lasers
Macrolides - pharmacology
MAP Kinase Signaling System
Mice
Microscopy, Confocal
Models, Biological
Monensin - pharmacology
NIH 3T3 Cells
Phosphorylation
Plasmids - metabolism
Protein Binding
Protein Biosynthesis
Protein Transport
Quinones - pharmacology
Signal Transduction
Subcellular Fractions
Time Factors
Transcription, Genetic
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M600477200