Formation of disulfide bridges drives oligomerization, membrane pore formation, and translocation of fibroblast growth factor 2 to cell surfaces
Fibroblast growth factor 2 (FGF2) is a key signaling molecule in tumor-induced angiogenesis. FGF2 is secreted by an unconventional secretory mechanism that involves phosphatidylinositol 4,5-bisphosphate-dependent insertion of FGF2 oligomers into the plasma membrane. This process is regulated by Tec...
Gespeichert in:
| Hauptverfasser: | , , , , , , , , , , |
|---|---|
| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
February 18, 2015
|
| In: |
The journal of biological chemistry
Year: 2015, Jahrgang: 290, Heft: 14, Pages: 8925-8937 |
| ISSN: | 1083-351X |
| DOI: | 10.1074/jbc.M114.622456 |
| Online-Zugang: | Verlag, Volltext: https://doi.org/10.1074/jbc.M114.622456 Verlag, Volltext: http://www.jbc.org/content/290/14/8925 
|
| Verfasserangaben: | Hans-Michael Müller, Julia P. Steringer, Sabine Wegehingel, Stephanie Bleicken, Maximilian Münster, Eleni Dimou, Sebastian Unger, Georg Weidmann, Helena Andreas, Ana J. García-Sáez, Klemens Wild, Irmgard Sinning, and Walter Nickel |
MARC
| LEADER | 00000caa a2200000 c 4500 | ||
|---|---|---|---|
| 001 | 1725603225 | ||
| 003 | DE-627 | ||
| 005 | 20230426183819.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 200727s2015 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1074/jbc.M114.622456 |2 doi | |
| 035 | |a (DE-627)1725603225 | ||
| 035 | |a (DE-599)KXP1725603225 | ||
| 035 | |a (OCoLC)1341347936 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rda | ||
| 041 | |a eng | ||
| 084 | |a 32 |2 sdnb | ||
| 100 | 1 | |a Müller, Hans-Michael |e VerfasserIn |0 (DE-588)1156241391 |0 (DE-627)1018709509 |0 (DE-576)502055901 |4 aut | |
| 245 | 1 | 0 | |a Formation of disulfide bridges drives oligomerization, membrane pore formation, and translocation of fibroblast growth factor 2 to cell surfaces |c Hans-Michael Müller, Julia P. Steringer, Sabine Wegehingel, Stephanie Bleicken, Maximilian Münster, Eleni Dimou, Sebastian Unger, Georg Weidmann, Helena Andreas, Ana J. García-Sáez, Klemens Wild, Irmgard Sinning, and Walter Nickel |
| 264 | 1 | |c February 18, 2015 | |
| 300 | |a 14 | ||
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a Computermedien |b c |2 rdamedia | ||
| 338 | |a Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Gesehen am 27.07.2020 | ||
| 520 | |a Fibroblast growth factor 2 (FGF2) is a key signaling molecule in tumor-induced angiogenesis. FGF2 is secreted by an unconventional secretory mechanism that involves phosphatidylinositol 4,5-bisphosphate-dependent insertion of FGF2 oligomers into the plasma membrane. This process is regulated by Tec kinase-mediated tyrosine phosphorylation of FGF2. Molecular interactions driving FGF2 monomers into membrane-inserted FGF2 oligomers are unknown. Here we identify two surface cysteines that are critical for efficient unconventional secretion of FGF2. They represent unique features of FGF2 as they are absent from all signal-peptide-containing members of the FGF protein family. We show that phosphatidylinositol 4,5-bisphosphate-dependent FGF2 oligomerization concomitant with the generation of membrane pores depends on FGF2 surface cysteines as either chemical alkylation or substitution with alanines impairs these processes. We further demonstrate that the FGF2 variant forms lacking the two surface cysteines are not secreted from cells. These findings were corroborated by experiments redirecting a signal-peptide-containing FGF family member from the endoplasmic reticulum/Golgi-dependent secretory pathway into the unconventional secretory pathway of FGF2. Cis elements known to be required for unconventional secretion of FGF2, including the two surface cysteines, were transplanted into a variant form of FGF4 without signal peptide. The resulting FGF4/2 hybrid protein was secreted by unconventional means. We propose that the formation of disulfide bridges drives membrane insertion of FGF2 oligomers as intermediates in unconventional secretion of FGF2. | ||
| 650 | 4 | |a Fibroblast Growth Factor (FGF) | |
| 650 | 4 | |a Fibroblast Growth Factor 2/FGF2 | |
| 650 | 4 | |a Inositol Phospholipid | |
| 650 | 4 | |a Membrane Pore Formation | |
| 650 | 4 | |a Membrane Recruitment and Translocation | |
| 650 | 4 | |a Phosphoinositides | |
| 650 | 4 | |a Plasma Membrane | |
| 650 | 4 | |a Protein Sorting | |
| 650 | 4 | |a Secretion | |
| 650 | 4 | |a Unconventional Protein Secretion | |
| 700 | 1 | |a Steringer, Julia P. |e VerfasserIn |0 (DE-588)1030135983 |0 (DE-627)734831730 |0 (DE-576)377942324 |4 aut | |
| 700 | 1 | |a Wegehingel, Sabine |e VerfasserIn |0 (DE-588)111215910X |0 (DE-627)866117032 |0 (DE-576)476411610 |4 aut | |
| 700 | 1 | |a Münster, Maximilian |e VerfasserIn |0 (DE-588)1186745959 |0 (DE-627)1666030449 |4 aut | |
| 700 | 1 | |a Dimou, Eleni |e VerfasserIn |0 (DE-588)1154609464 |0 (DE-627)1016032900 |0 (DE-576)501146407 |4 aut | |
| 700 | 1 | |a Unger, Sebastian |e VerfasserIn |0 (DE-588)1157035302 |0 (DE-627)1020031530 |0 (DE-576)502586303 |4 aut | |
| 700 | 1 | |a Weidmann, Georg |e VerfasserIn |0 (DE-588)1214610714 |0 (DE-627)1725601834 |4 aut | |
| 700 | 1 | |a Andreas, Helena |e VerfasserIn |0 (DE-588)1156239222 |0 (DE-627)101870311X |0 (DE-576)502052139 |4 aut | |
| 700 | 1 | |a Wild, Klemens |e VerfasserIn |0 (DE-588)1049291190 |0 (DE-627)781602394 |0 (DE-576)177410892 |4 aut | |
| 700 | 1 | |a Sinning, Irmgard |d 1960- |e VerfasserIn |0 (DE-588)1027598617 |0 (DE-627)72945133X |0 (DE-576)166290580 |4 aut | |
| 700 | 1 | |a Nickel, Walter |e VerfasserIn |0 (DE-588)1060271311 |0 (DE-627)799356964 |0 (DE-576)416359817 |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t The journal of biological chemistry |d [Amsterdam] : Elsevier B.V., 1905 |g 290(2015), 14, Seite 8925-8937 |h Online-Ressource |w (DE-627)269247025 |w (DE-600)1474604-9 |w (DE-576)077883837 |x 1083-351X |7 nnas |a Formation of disulfide bridges drives oligomerization, membrane pore formation, and translocation of fibroblast growth factor 2 to cell surfaces |
| 773 | 1 | 8 | |g volume:290 |g year:2015 |g number:14 |g pages:8925-8937 |g extent:14 |a Formation of disulfide bridges drives oligomerization, membrane pore formation, and translocation of fibroblast growth factor 2 to cell surfaces |
| 856 | 4 | 0 | |u https://doi.org/10.1074/jbc.M114.622456 |x Verlag |x Resolving-System |3 Volltext |
| 856 | 4 | 0 | |u http://www.jbc.org/content/290/14/8925 |x Verlag |3 Volltext |
| 951 | |a AR | ||
| 992 | |a 20200727 | ||
| 993 | |a Article | ||
| 994 | |a 2015 | ||
| 998 | |g 1060271311 |a Nickel, Walter |m 1060271311:Nickel, Walter |d 700000 |d 711000 |e 700000PN1060271311 |e 711000PN1060271311 |k 0/700000/ |k 1/700000/711000/ |p 13 |y j | ||
| 998 | |g 1027598617 |a Sinning, Irmgard |m 1027598617:Sinning, Irmgard |d 700000 |d 711000 |e 700000PS1027598617 |e 711000PS1027598617 |k 0/700000/ |k 1/700000/711000/ |p 12 | ||
| 998 | |g 1049291190 |a Wild, Klemens |m 1049291190:Wild, Klemens |d 700000 |d 711000 |e 700000PW1049291190 |e 711000PW1049291190 |k 0/700000/ |k 1/700000/711000/ |p 11 | ||
| 998 | |g 1156239222 |a Andreas, Helena |m 1156239222:Andreas, Helena |p 9 | ||
| 998 | |g 1214610714 |a Weidmann, Georg |m 1214610714:Weidmann, Georg |p 8 | ||
| 998 | |g 1157035302 |a Unger, Sebastian |m 1157035302:Unger, Sebastian |d 500000 |d 510083 |e 500000PU1157035302 |e 510083PU1157035302 |k 0/500000/ |k 1/500000/510083/ |p 7 | ||
| 998 | |g 1154609464 |a Dimou, Eleni |m 1154609464:Dimou, Eleni |d 500000 |d 510083 |e 500000PD1154609464 |e 510083PD1154609464 |k 0/500000/ |k 1/500000/510083/ |p 6 | ||
| 998 | |g 1186745959 |a Münster, Maximilian |m 1186745959:Münster, Maximilian |d 140000 |d 140001 |e 140000PM1186745959 |e 140001PM1186745959 |k 0/140000/ |k 1/140000/140001/ |p 5 | ||
| 998 | |g 111215910X |a Wegehingel, Sabine |m 111215910X:Wegehingel, Sabine |d 700000 |d 711000 |e 700000PW111215910X |e 711000PW111215910X |k 0/700000/ |k 1/700000/711000/ |p 3 | ||
| 998 | |g 1030135983 |a Steringer, Julia P. |m 1030135983:Steringer, Julia P. |d 700000 |d 711000 |e 700000PS1030135983 |e 711000PS1030135983 |k 0/700000/ |k 1/700000/711000/ |p 2 | ||
| 998 | |g 1156241391 |a Müller, Hans-Michael |m 1156241391:Müller, Hans-Michael |d 700000 |d 711000 |e 700000PM1156241391 |e 711000PM1156241391 |k 0/700000/ |k 1/700000/711000/ |p 1 |x j | ||
| 999 | |a KXP-PPN1725603225 |e 3729517341 | ||
| BIB | |a Y | ||
| SER | |a journal | ||
| JSO | |a {"origin":[{"dateIssuedDisp":"February 18, 2015","dateIssuedKey":"2015"}],"relHost":[{"title":[{"subtitle":"JBC","title":"The journal of biological chemistry","title_sort":"journal of biological chemistry"}],"physDesc":[{"extent":"Online-Ressource"}],"id":{"zdb":["1474604-9"],"issn":["1083-351X"],"eki":["269247025"]},"origin":[{"publisherPlace":"[Amsterdam] ; Baltimore, Md. [u.a.] ; Bethesda, Md.","dateIssuedKey":"2021","dateIssuedDisp":"2021-","publisher":"Elsevier B.V. ; American Soc. of Biological Chemists ; ASBMB Publications"}],"name":{"displayForm":["publ. by the American Society for Biochemistry and Molecular Biology"]},"recId":"269247025","disp":"Formation of disulfide bridges drives oligomerization, membrane pore formation, and translocation of fibroblast growth factor 2 to cell surfacesThe journal of biological chemistry","type":{"media":"Online-Ressource","bibl":"periodical"},"corporate":[{"role":"isb","display":"American Society for Biochemistry and Molecular Biology"}],"titleAlt":[{"title":"JBC online"},{"title":"JBC"}],"language":["eng"],"part":{"volume":"290","year":"2015","text":"290(2015), 14, Seite 8925-8937","pages":"8925-8937","extent":"14","issue":"14"},"pubHistory":["1.1905/06 -"],"note":["Gesehen am 19.05.2021"]}],"id":{"eki":["1725603225"],"doi":["10.1074/jbc.M114.622456"]},"physDesc":[{"extent":"14 S."}],"type":{"media":"Online-Ressource","bibl":"article-journal"},"title":[{"title":"Formation of disulfide bridges drives oligomerization, membrane pore formation, and translocation of fibroblast growth factor 2 to cell surfaces","title_sort":"Formation of disulfide bridges drives oligomerization, membrane pore formation, and translocation of fibroblast growth factor 2 to cell surfaces"}],"note":["Gesehen am 27.07.2020"],"person":[{"display":"Müller, Hans-Michael","given":"Hans-Michael","role":"aut","family":"Müller"},{"given":"Julia P.","display":"Steringer, Julia P.","family":"Steringer","role":"aut"},{"family":"Wegehingel","role":"aut","given":"Sabine","display":"Wegehingel, Sabine"},{"given":"Maximilian","display":"Münster, Maximilian","family":"Münster","role":"aut"},{"role":"aut","family":"Dimou","display":"Dimou, Eleni","given":"Eleni"},{"role":"aut","family":"Unger","given":"Sebastian","display":"Unger, Sebastian"},{"role":"aut","family":"Weidmann","display":"Weidmann, Georg","given":"Georg"},{"display":"Andreas, Helena","given":"Helena","family":"Andreas","role":"aut"},{"display":"Wild, Klemens","given":"Klemens","role":"aut","family":"Wild"},{"role":"aut","family":"Sinning","given":"Irmgard","display":"Sinning, Irmgard"},{"given":"Walter","display":"Nickel, Walter","family":"Nickel","role":"aut"}],"recId":"1725603225","name":{"displayForm":["Hans-Michael Müller, Julia P. Steringer, Sabine Wegehingel, Stephanie Bleicken, Maximilian Münster, Eleni Dimou, Sebastian Unger, Georg Weidmann, Helena Andreas, Ana J. García-Sáez, Klemens Wild, Irmgard Sinning, and Walter Nickel"]},"language":["eng"]} | ||
| SRT | |a MUELLERHANFORMATIONO1820 | ||