FGF-1 and FGF-2 require the cytosolic chaperone Hsp90 for translocation into the cytosol and the cell nucleus

Jørgen Wesche; Jedrzej Małecki; Antoni Wiedłocha; Camilla Skiple Skjerpen; Peter Claus; Sjur Olsnes

doi:10.1074/jbc.M600477200

FGF-1 and FGF-2 require the cytosolic chaperone Hsp90 for translocation into the cytosol and the cell nucleus

J Biol Chem. 2006 Apr 21;281(16):11405-12. doi: 10.1074/jbc.M600477200. Epub 2006 Feb 22.

Authors

Jørgen Wesche¹, Jedrzej Małecki, Antoni Wiedłocha, Camilla Skiple Skjerpen, Peter Claus, Sjur Olsnes

Affiliation

¹ Institute for Cancer Research at the Norwegian Radium Hospital, University of Oslo, Montebello, 0310 Oslo, Norway. jorgen.wesche@labmed.uio.no

PMID: 16495214
DOI: 10.1074/jbc.M600477200

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

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*
HSP90 Heat-Shock Proteins / metabolism*
Heparin / pharmacology
Humans
Lactams, Macrocyclic
Lactones / pharmacology
Lasers
MAP Kinase Signaling System
Macrolides / pharmacology
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

Substances

Benzoquinones
HSP90 Heat-Shock Proteins
Lactams, Macrocyclic
Lactones
Macrolides
Quinones
Fibroblast Growth Factor 2
Fibroblast Growth Factor 1
bafilomycin A1
Heparin
Monensin
monorden
geldanamycin