Inhibition of tyrosine phosphatases induces apoptosis independent from the CD95 system

• Verfasst von: Hehner, Steffen Peter [VerfasserIn]
• Verfasst von: Hofmann, Thomas G. [VerfasserIn]
• Verfasst von: Dröge, Wulf [VerfasserIn]
• Titel: Inhibition of tyrosine phosphatases induces apoptosis independent from the CD95 system
• Verf.angabe: Steffen P. Hehner, Thomas G. Hofmann, Wulf Dröge and M. Lienhard Schmitz
• E-Jahr: 1999
• Jahr: 29 September 1999
• Umfang: 9 S.
• Fussnoten: Gesehen am 09.02.2021
• Titel Quelle: Enthalten in: Cell death and differentiation
• Ort Quelle: Houndmills, Basingstoke : Nature Publishing Group, 1997
• Jahr Quelle: 1999
• Band/Heft Quelle: 6(1999), 9, Seite 833-841
• ISSN Quelle: 1476-5403
• DOI: doi:10.1038/sj.cdd.4400559
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1747806617

Abstract

The inhibition of protein tyrosine phosphatases by pervanadate, a potent activator of B- and T-cells through the induction of tyrosine phosphorylation and downstream signaling events in different activation cascades, efficiently induced apoptosis in lymphoid cell lines. Pervanadate-elicited apoptosis could be blocked by the tyrosine kinase inhibitor herbimycin A. This apoptotic process involved the activation of caspases 3, 8 and 9, the induction of mitochondrial permeability transition, the release of cytochrome C and the fragmentation of chromosomal DNA. T-cells lacking the CD95 receptor or caspase-8 and T-cells stably overexpressing a transdominant negative form of the adaptor protein FADD were still susceptible to pervanadate-induced apoptosis, excluding the involvement of the CD95 system or other FADD-dependent death receptors. The apoptotic program initiated by the inhibition of tyrosine phosphatases did not require the presence of the tyrosine kinase p56lck or phosphatase CD45, whereas Bcl-2 overexpression protected T-cells from pervanadate-induced cytochrome C release, caspase-8 cleavage and apoptosis.