Inhibition of tyrosine phosphatases induces apoptosis independent from the CD95 system

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 apoptosi...

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Hauptverfasser: Hehner, Steffen Peter (VerfasserIn) , Hofmann, Thomas G. (VerfasserIn) , Dröge, Wulf (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 29 September 1999
In: Cell death and differentiation
Year: 1999, Jahrgang: 6, Heft: 9, Pages: 833-841
ISSN:1476-5403
DOI:10.1038/sj.cdd.4400559
Online-Zugang:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1038/sj.cdd.4400559
Verlag, lizenzpflichtig, Volltext: https://www.nature.com/articles/4400559
Volltext
Verfasserangaben:Steffen P. Hehner, Thomas G. Hofmann, Wulf Dröge and M. Lienhard Schmitz
Beschreibung
Zusammenfassung: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.
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Beschreibung:Online Resource
ISSN:1476-5403
DOI:10.1038/sj.cdd.4400559