Journal article
p56Lck Tyrosine Kinase Enhances the Assembly of Death-inducing Signaling Complex during Fas-mediated Apoptosis
The Journal of biological chemistry, v 282(49), pp 36048-36056
07 Dec 2007
PMID: 17932036
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Although the death-inducing signaling complex (DISC) is rapidly assembled, several lines of evidence suggest that formation of this complex is not the first consequence of cell surface CD95 (Fas) stimulation but rather a later step in this process. Activation of Fas triggers a cascade of signaling events that culminate in cellular apoptosis. Tyrosine kinases are critical effectors in T cell activation. However, their functional involvement in death receptor-mediated apoptosis is unknown. Here, we used p56Lck-deficient cells to show that CD95-induced cell death is highly dependent on p56Lck activity and its localization within plasma membrane. We found that p56Lck acts upstream of the mitochondria; in the absence of p56Lck, Bid cleavage and the release of cytochrome c were severely impaired. Moreover, p56Lck-deficient cells or cells expressing an inactive form of p56Lck displayed defective formation of the DISC post CD95 stimulation. In vivo reconstitution of thymocytes from p56lck-deficient mice, which are resistant to apoptosis, with p56Lck restored Fas-mediated cell death. Our results support a novel model whereby sensitivity to apoptosis is regulated through quantitative changes in the stoichiometry of DISC components triggered by p56Lck activation and localization.
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Details
- Title
- p56Lck Tyrosine Kinase Enhances the Assembly of Death-inducing Signaling Complex during Fas-mediated Apoptosis
- Creators
- Ehssan Sharif-Askari - Université de MontréalDenis Gaucher - Université de MontréalRabih Halwani - Université de MontréalJennifer Ma - Hôpital Saint-LucKevin Jao - Hôpital Saint-LucAli Abdallah - Hôpital Saint-LucElias K. Haddad - Laboratoire d'Immunologie, Centre de Recherche CHUM Saint-Luc, Montréal H2X 1P1Rafick-Pierre Sékaly - Hôpital Saint-Luc
- Publication Details
- The Journal of biological chemistry, v 282(49), pp 36048-36056
- Publisher
- Elsevier
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- College of Medicine; Infectious Diseases (and HIV Medicine); Drexel University
- Web of Science ID
- WOS:000251458100064
- Scopus ID
- 2-s2.0-37249073299
- Other Identifier
- 991020100190804721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Biochemistry & Molecular Biology