Cell-Surface Heparan Sulfate Proteoglycans Are Essential Components of the Unconventional Export Machinery of FGF-2
FGF-2 is an unconventionally secreted lectin that transmits proangiogenic signals through a ternary complex with high-affinity FGF receptors and heparan sulfate proteoglycans (HSPGs). Although FGF-2 signal transduction is understood in great detail, its mechanism of release from cells, which is inde...
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| Veröffentlicht in: | Proceedings of the National Academy of Sciences - PNAS 2006-10, Vol.103 (42), p.15479-15484 |
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| container_title | Proceedings of the National Academy of Sciences - PNAS |
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| creator | Zehe, Christoph Engling, André Wegehingel, Sabine Schäfer, Tobias Nickel, Walter |
| description | FGF-2 is an unconventionally secreted lectin that transmits proangiogenic signals through a ternary complex with high-affinity FGF receptors and heparan sulfate proteoglycans (HSPGs). Although FGF-2 signal transduction is understood in great detail, its mechanism of release from cells, which is independent of the classical secretory pathway, remains elusive. To test the hypothesis that FGF-2 secretion is linked to its cell-surface ligands, we studied FGF-2 release using mutants defective for HSPG binding and cells with impaired HSPG biosynthesis. Here, we report that a functional interaction between FGF-2 and HSPGs is required for net export of FGF-2 from mammalian cells. FGF-2 release requires extracellular, membrane-proximal HSPGs. We propose that extracellular HSPGs form a molecular trap that drives FGF-2 translocation across the plasma membrane. |
| doi_str_mv | 10.1073/pnas.0605997103 |
| format | Article |
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Although FGF-2 signal transduction is understood in great detail, its mechanism of release from cells, which is independent of the classical secretory pathway, remains elusive. To test the hypothesis that FGF-2 secretion is linked to its cell-surface ligands, we studied FGF-2 release using mutants defective for HSPG binding and cells with impaired HSPG biosynthesis. Here, we report that a functional interaction between FGF-2 and HSPGs is required for net export of FGF-2 from mammalian cells. FGF-2 release requires extracellular, membrane-proximal HSPGs. 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| subjects | Animals Antibodies Biological Sciences Cell lines Cell Membrane - chemistry Cell Membrane - metabolism Cell membranes Cells Cellular communications CHO Cells Coculture Techniques Cricetinae Cytometry Fibroblast Growth Factor 2 - genetics Fibroblast Growth Factor 2 - metabolism Fluorescence Heparan Sulfate Proteoglycans - chemistry Heparan Sulfate Proteoglycans - metabolism Heparin Molecules Protein Binding Protein Transport - physiology Proteins Recombinant Fusion Proteins - genetics Recombinant Fusion Proteins - metabolism Secretion Signal transduction Signal Transduction - physiology Sugar |
| title | Cell-Surface Heparan Sulfate Proteoglycans Are Essential Components of the Unconventional Export Machinery of FGF-2 |
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