Tec-kinase-mediated phosphorylation of fibroblast growth factor 2 is essential for unconventional secretion
Fibroblast growth factor 2 (FGF2) is a potent mitogen that is exported from cells by an endoplasmic reticulum (ER)/Golgi-independent mechanism. Unconventional secretion of FGF2 occurs by direct translocation across plasma membranes, a process that depends on the phosphoinositide phosphatidylinositol...
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| Main Authors: | , , , , , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
10 May 2010
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| In: |
Traffic
Year: 2010, Volume: 11, Issue: 6, Pages: 813-826 |
| ISSN: | 1600-0854 |
| DOI: | 10.1111/j.1600-0854.2010.01059.x |
| Online Access: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1111/j.1600-0854.2010.01059.x Verlag, lizenzpflichtig, Volltext: https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1600-0854.2010.01059.x 
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| Author Notes: | Antje D. Ebert, Mareike Laußmann, Sabine Wegehingel, Lars Kaderali, Holger Erfle, Jürgen Reichert, Johannes Lechner, Hans-Dietmar Beer, Rainer Pepperkok and Walter Nickel |
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| 520 | |a Fibroblast growth factor 2 (FGF2) is a potent mitogen that is exported from cells by an endoplasmic reticulum (ER)/Golgi-independent mechanism. Unconventional secretion of FGF2 occurs by direct translocation across plasma membranes, a process that depends on the phosphoinositide phosphatidylinositol 4,5-biphosphate (PI(4,5)P2) at the inner leaflet as well as heparan sulfate proteoglycans at the outer leaflet of plasma membranes; however, additional core and regulatory components of the FGF2 export machinery have remained elusive. Here, using a highly effective RNAi screening approach, we discovered Tec kinase as a novel factor involved in unconventional secretion of FGF2. Tec kinase does not affect FGF2 secretion by an indirect mechanism, but rather forms a heterodimeric complex with FGF2 resulting in phosphorylation of FGF2 at tyrosine 82, a post-translational modification shown to be essential for FGF2 membrane translocation to cell surfaces. Our findings suggest a crucial role for Tec kinase in regulating FGF2 secretion under various physiological conditions and, therefore, provide a new perspective for the development of a novel class of antiangiogenic drugs targeting the formation of the FGF2/Tec complex. | ||
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