title: Vanadate-induced inhibition of BCR-triggered apoptosis is coupled with tyrosine phosphorylation and induction of G2M growth arrest in Ramos-BL B cells.
abstract: 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.
authors.affiliation: Department of Biochemistry, South Parks Road, University of Oxford, UK.
authors.forename: Kroum K
authors.initials: KK
authors.lastname: Hristov
authors.forename: Kirstine A
authors.initials: KA
authors.lastname: Knox
authors.forename: Vanio I
authors.initials: VI
authors.lastname: Mitev
mesh_terms: D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D001402:B-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D002051:Burkitt Lymphoma / Q000473:pathology; D002455:Cell Division / Q000187:drug effects*; D016195:G2 Phase / Q000187:drug effects*; D051562:Proto-Oncogene Proteins c-bcr / Q000502:physiology*; D011947:Receptors, Antigen, B-Cell / Q000276:immunology; D015398:Signal Transduction; D014443:Tyrosine / Q000378:metabolism*; D014638:Vanadates / Q000494:pharmacology*
chemical_list: D011947:Receptors, Antigen, B-Cell; D014638:Vanadates; D014443:Tyrosine; C496613:BCR protein, human; D051562:Proto-Oncogene Proteins c-bcr