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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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Main Authors: Steringer, Julia P. (Author) , Zacherl, Sonja (Author) , Andreas, Helena (Author) , Laußmann, Mareike (Author) , Temmerman, Koen (Author) , Contreras, F. Xabier (Author) , Lechner, Johannes (Author) , Müller, Hans-Michael (Author) , García-Sáez, Ana J. (Author) , Nickel, Walter (Author)
Format: Article (Journal)
Language:English
Published: June 23, 2012
In: The journal of biological chemistry
Year: 2012, Volume: 287, Issue: 33, Pages: 27659-27669
ISSN:1083-351X
DOI:10.1074/jbc.M112.381939
Online Access: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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Author Notes: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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Summary: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.
Item Description:Gesehen am 16.04.2018
Im Titel ist bei (PI(4,5)P2) die Ziffer "2" tiefgestellt
Physical Description:Online Resource
ISSN:1083-351X
DOI:10.1074/jbc.M112.381939

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