| Titel: | Role for Tyrosine Kinase Lck in regulation of Apoptotic Pathways |
| URL für Lesezeichen: | https://docserv.uni-duesseldorf.de/servlets/DocumentServlet?id=3079 |
| URN (NBN): | urn:nbn:de:hbz:061-20050427-001079-5 |
| Kollektion: | Dissertationen |
| Sprache: | Englisch |
| Dokumententyp: | Wissenschaftliche Abschlussarbeiten » Dissertation |
| Medientyp: | Text |
| Autor: | Samraj, Ajoy Kumar [Autor]
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| Dateien: | |
| Beitragender: | Prof. Dr. Mehlhorn, Hans-Peter Heinz [Gutachter]
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| Stichwörter: | Apoptosis, Lck |
| Dewey Dezimal-Klassifikation: | 500 Naturwissenschaften und Mathematik » 570 Biowissenschaften; Biologie |
| Beschreibung: | Tyrosine kinases of the Src family have been implicated in key biological processes. Here we report that p56Lck, a lymphoid-specific Src kinase, plays a crucial role for the activation of the mitochondrial apoptosis pathway. Lck-deficient Jurkat T-cells were completey resistant to anticancer drugs. In contrast, apoptosis sensitivity to death receptors such as CD95 was not altered, indicating that a specific interference of Lck with the mitochondrial pathway. Reexpression of Lck restored sensitivity to drug-induced apoptosis and triggered mitochondrial cytochrome c release and subsequent caspase activation. Further analysis identified that sensitization by Lck was independent of stress-activated protein kinases and classical mediators of T cell receptor signaling, but essentially involved the Bcl-2 member Bak. Expression of Bak was completely absent in Lck-deficient cells, while, importantly, reexpression of Lck transcriptionally triggered Bak expression and conferred sensitivity to drug-induced apoptosis, which was associated with a proapoptotic conformational change of Bak. Furthermore, in vitro the truncated fragment of Bid specifically activated Bak and cytochrome c release only from mitochondria of Lck expressing cells. These results do not only demonstrate a sentinal role of Lck in drug resistance, but also delineate a hitherto unknown pathway of Src kinases in regulation of expression of Bcl-2 proteins.
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| Lizenz: | 
Urheberrechtsschutz
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| Fachbereich / Einrichtung: | Mathematisch- Naturwissenschaftliche Fakultät » WE Biologie |
| Dokument erstellt am: | 27.04.2005 |
| Dateien geändert am: | 12.02.2007 |
| Promotionsantrag am: | 20.01.2005 |
| Datum der Promotion: | 20.01.2005 |
