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• W2230483323 endingPage "598" @default.
• W2230483323 startingPage "590" @default.
• W2230483323 abstract "The signalling pathways that arrest the cell cycle and trigger cell death are only partially known. Dimerization of CD38, a 45-kD transmembrane type II glycoprotein highly expressed in immature B cells, inhibits cell growth and causes apoptosis in normal and leukemic B-cell progenitors, but the molecular mechanisms underlying these cellular responses are unknown. In the present study, we found that CD38 ligation in the immature B-cell lines 380, REH, and RS4;11 caused rapid tyrosine phosphorylation of the protein product of the proto- oncogene c-cbl. Dimerization of CD38 was accompanied by the association of cbl with the p85 subunit of phosphatidylinositol 3-kinase (Pl 3-K), resulting in markedly increased Pl 3-K activity in antiphosphotyrosine and anti-cbl immunoprecipitates. Wortmannin and LY294002, two potent inhibitors of Pl 3-K, rescued immature B cells from CD38-mediated growth suppression. This effect was observed not only in model B-cell lines, but also in cultures of leukemic lymphoblasts from patients, and in normal bone marrow B-cell progenitors as well. Concentrations of inhibitors that reversed cellular responses to CD38 significantly decreased Pl 3-K activity. By contrast, rapamycin, a p70 S6-kinase inhibitor, did not rescue immature B cells from CD38-mediated suppression. These results suggest that Pl 3-K activity is essential for CD38-mediated inhibition of lymphopoiesis and that cbl and Pl 3-K are regulatory molecules whose activation can result in suppression of cell proliferation and apoptosis in immature lymphoid cells." @default.
• W2230483323 created "2016-06-24" @default.
• W2230483323 creator A5062238503 @default.
• W2230483323 creator A5065331155 @default.
• W2230483323 creator A5084765813 @default.
• W2230483323 creator A5091145269 @default.
• W2230483323 date "1996-07-15" @default.
• W2230483323 modified "2023-10-03" @default.
• W2230483323 title "CD38-mediated growth suppression of B-cell progenitors requires activation of phosphatidylinositol 3-kinase and involves its association with the protein product of the c-cbl proto-oncogene" @default.
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• W2230483323 doi "https://doi.org/10.1182/blood.v88.2.590.bloodjournal882590" @default.
• W2230483323 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/8695807" @default.
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