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Status: Bibliographieeintrag

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Verfasst von:La Venuta, Giuseppe [VerfasserIn]   i
 Wegehingel, Sabine [VerfasserIn]   i
 Sehr, Peter [VerfasserIn]   i
 Müller, Hans-Michael [VerfasserIn]   i
 Dimou, Eleni [VerfasserIn]   i
 Steringer, Julia Pauline [VerfasserIn]   i
 Grotwinkel, Mareike [VerfasserIn]   i
 Hentze, Nikolai [VerfasserIn]   i
 Mayer, Matthias P. [VerfasserIn]   i
 Will, David W. [VerfasserIn]   i
 Uhrig, Ulrike [VerfasserIn]   i
 Lewis, Joe D. [VerfasserIn]   i
 Nickel, Walter [VerfasserIn]   i
Titel:Small molecule inhibitors targeting tec kinase block unconventional secretion of fibroblast growth factor 2
Verf.angabe:Giuseppe La Venuta, Sabine Wegehingel, Peter Sehr, Hans-Michael Müller, Eleni Dimou, Julia P. Steringer, Mareike Grotwinkel, Nikolai Hentze, Matthias P. Mayer, David W. Will, Ulrike Uhrig, Joe D. Lewis, and Walter Nickel
E-Jahr:2016
Jahr:July 5, 2016
Umfang:17 S.
Fussnoten:Gesehen am 08.06.2020
Titel Quelle:Enthalten in: The journal of biological chemistry
Ort Quelle:Bethesda, Md. : Soc., 1905
Jahr Quelle:2016
Band/Heft Quelle:291(2016), 34, Seite 17787-17803
ISSN Quelle:1083-351X
Abstract:Fibroblast growth factor 2 (FGF2) is a potent mitogen promoting both tumor cell survival and tumor-induced angiogenesis. It is secreted by an unconventional secretory mechanism that is based upon direct translocation across the plasma membrane. Key steps of this process are (i) phosphoinositide-dependent membrane recruitment, (ii) FGF2 oligomerization and membrane pore formation, and (iii) extracellular trapping mediated by membrane-proximal heparan sulfate proteoglycans. Efficient secretion of FGF2 is supported by Tec kinase that stimulates membrane pore formation based upon tyrosine phosphorylation of FGF2. Here, we report the biochemical characterization of the direct interaction between FGF2 and Tec kinase as well as the identification of small molecules that inhibit (i) the interaction of FGF2 with Tec, (ii) tyrosine phosphorylation of FGF2 mediated by Tec in vitro and in a cellular context, and (iii) unconventional secretion of FGF2 from cells. We further demonstrate the specificity of these inhibitors for FGF2 because tyrosine phosphorylation of a different substrate of Tec is unaffected in their presence. Building on previous evidence using RNA interference, the identified compounds corroborate the role of Tec kinase in unconventional secretion of FGF2. In addition, they are valuable lead compounds with great potential for drug development aiming at the inhibition of FGF2-dependent tumor growth and metastasis.
DOI:doi:10.1074/jbc.M116.729384
URL:Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.

Volltext ; Verlag: https://doi.org/10.1074/jbc.M116.729384
 Volltext: http://www.jbc.org/content/291/34/17787
 DOI: https://doi.org/10.1074/jbc.M116.729384
Datenträger:Online-Ressource
Sprache:eng
Sach-SW:FGF2
 fibroblast growth factor (FGF)
 phosphoinositide
 protein phosphorylation
 protein secretion
 protein translocation
 protein translocation across membranes
 Tec kinase
 unconventional protein secretion
K10plus-PPN:1700115855
Verknüpfungen:→ Zeitschrift

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