Phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2)-dependent oligomerization of fibroblast growth factor 2 (FGF2) triggers the formation of a lipidic membrane pore implicated in unconventional secretion
Fibroblast growth factor 2 (FGF2) is a critical mitogen with a central role in specific steps of tumor-induced angiogenesis. It is known to be secreted by unconventional means bypassing the endoplasmic reticulum/Golgi-dependent secretory pathway. However, the mechanism of FGF2 membrane translocation...
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| Hauptverfasser: | , , , , , , , , , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
June 23, 2012
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| In: |
The journal of biological chemistry
Year: 2012, Jahrgang: 287, Heft: 33, Pages: 27659-27669 |
| ISSN: | 1083-351X |
| DOI: | 10.1074/jbc.M112.381939 |
| Online-Zugang: | Verlag, LF, Volltext: http://dx.doi.org/10.1074/jbc.M112.381939 Verlag, LF, Volltext: http://www.jbc.org/content/287/33/27659 
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| Verfasserangaben: | Julia P. Steringer, Stephanie Bleicken, Helena Andreas, Sonja Zacherl, Mareike Laussmann, Koen Temmerman, F. Xabier Contreras, Tanmay A.M. Bharat, Johannes Lechner, Hans-Michael Müller, John A.G. Briggs, Ana J. García-Sáez, and Walter Nickel |
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| 245 | 1 | 0 | |a Phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2)-dependent oligomerization of fibroblast growth factor 2 (FGF2) triggers the formation of a lipidic membrane pore implicated in unconventional secretion |c Julia P. Steringer, Stephanie Bleicken, Helena Andreas, Sonja Zacherl, Mareike Laussmann, Koen Temmerman, F. Xabier Contreras, Tanmay A.M. Bharat, Johannes Lechner, Hans-Michael Müller, John A.G. Briggs, Ana J. García-Sáez, and Walter Nickel |
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| 520 | |a Fibroblast growth factor 2 (FGF2) is a critical mitogen with a central role in specific steps of tumor-induced angiogenesis. It is known to be secreted by unconventional means bypassing the endoplasmic reticulum/Golgi-dependent secretory pathway. However, the mechanism of FGF2 membrane translocation into the extracellular space has remained elusive. Here, we show that phosphatidylinositol 4,5-bisphosphate-dependent membrane recruitment causes FGF2 to oligomerize, which in turn triggers the formation of a lipidic membrane pore with a putative toroidal structure. This process is strongly up-regulated by tyrosine phosphorylation of FGF2. Our findings explain key requirements of FGF2 secretion from living cells and suggest a novel self-sustained mechanism of protein translocation across membranes with a lipidic membrane pore being a transient translocation intermediate. | ||
| 650 | 4 | |a Fibroblast Growth Factor 2 | |
| 650 | 4 | |a Lipid-binding Protein | |
| 650 | 4 | |a Membrane Lipids | |
| 650 | 4 | |a Membrane Reconstitution | |
| 650 | 4 | |a Membrane Structure | |
| 650 | 4 | |a Phosphoinositides | |
| 650 | 4 | |a Protein Translocation across Membranes | |
| 650 | 4 | |a Transport | |
| 650 | 4 | |a Tyrosine Phosphorylation | |
| 650 | 4 | |a Unconventional Secretion | |
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