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Translocation of FGF-1 and FGF-2 across vesicular membranes occurs during G1-phase by a common mechanism.
- Source :
-
Molecular biology of the cell [Mol Biol Cell] 2004 Feb; Vol. 15 (2), pp. 801-14. Date of Electronic Publication: 2003 Dec 02. - Publication Year :
- 2004
-
Abstract
- The entry of exogenous fibroblast growth factor 2 (FGF-2) to the cytosolic/nuclear compartment was studied and compared with the translocation mechanism used by FGF-1. To differentiate between external and endogenous growth factor, we used FGF-2 modified to contain a farnesylation signal, a CaaX-box. Because farnesylation occurs only in the cytosol and nucleoplasm, farnesylation of exogenous FGF-2-CaaX was taken as evidence that the growth factor had translocated across cellular membranes. We found that FGF-2 translocation occurred in endothelial cells and fibroblasts, which express FGF receptors, and that the efficiency of translocation was increased in the presence of heparin. Concomitantly with translocation, the 18-kDa FGF-2 was N-terminally cleaved to yield a 16-kDa form. Translocation of FGF-2 required PI3-kinase activity but not transport through the Golgi apparatus. Inhibition of endosomal acidification did not prevent translocation, whereas dissipation of the vesicular membrane potential completely blocked it. The data indicate that translocation occurs from intracellular vesicles containing proton pumps and that an electrical potential across the vesicle membrane is required. Translocation of both FGF-1 and FGF-2 occurred during most of G(1) but decreased shortly before the G(1)-->S transition. A common mechanism for FGF-1 and FGF-2 translocation into cells is postulated.
- Subjects :
- 3T3 Cells
Animals
Cells, Cultured
Cytoplasmic Vesicles drug effects
Endothelial Cells drug effects
Endothelial Cells metabolism
Fibroblasts drug effects
Fibroblasts metabolism
G1 Phase physiology
Golgi Apparatus drug effects
Heparin pharmacology
Membrane Potentials physiology
Mice
Phosphatidylinositol 3-Kinases metabolism
Protein Prenylation drug effects
Protein Prenylation physiology
Protein Transport drug effects
Receptors, Fibroblast Growth Factor metabolism
Recombinant Proteins metabolism
Cytoplasmic Vesicles metabolism
Fibroblast Growth Factor 1 metabolism
Fibroblast Growth Factor 2 metabolism
Golgi Apparatus metabolism
Protein Transport physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1059-1524
- Volume :
- 15
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Molecular biology of the cell
- Publication Type :
- Academic Journal
- Accession number :
- 14657241
- Full Text :
- https://doi.org/10.1091/mbc.e03-08-0589