Vanadate-induced inhibition of BCR-triggered apoptosis is coupled with tyrosine phosphorylation and induction of G2M growth arrest in Ramos-BL B cells.

Autor: Hristov KK; Department of Biochemistry, South Parks Road, University of Oxford, UK., Knox KA, Mitev VI
Jazyk: angličtina
Zdroj: Immunological investigations [Immunol Invest] 2007; Vol. 36 (3), pp. 293-306.
DOI: 10.1080/08820130601069814
Abstrakt: The regulation of the tyrosine phosphorylation of key signaling molecules by tyrosine kinases and phosphatases is essential for BCR-triggered signaling cascades during B cell selection process. We used the non-selective tyrosine phosphatase inhibitor vanadate to study the importance of the late regulation of the tyrosine phosphorylation for BCR-triggered G1 growth arrest and apoptosis in Ramos-BL B cells. Vanadate induces G2M growth arrest in a dose-dependent manner and prevents BCR-triggered apoptosis. Vanadate-induced upregulation of the tyrosine phosphorylation is concomitant with increased expression of cyclin B and inhibition of caspase-3 activation and PARP cleavage. The anti-apoptotic effect of vanadate was observed even when added up to 6 hours after the treatment of Ramos-BL B cells with anti-IgM. Vanadate increases BCR-triggered tyrosine phosphorylation of the cytosolic tyrosine phosphatases, SHP-1 and SHP-2 after 24 hours. Co-stimulation with anti-CD40 prevents anti-IgM-triggered tyrosine phosphorylation of these phosphatases and up-regulates the expression of SHP-1. We conclude that the regulation of the tyrosine phosphatase activity is indispensable for BCR-triggered execution of the apoptosis in Ramos-BL B cells.
Databáze: MEDLINE
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