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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
A Kitanaka, C Ito, H Nishigaki and D Campana
Department of Hematology-Oncology, St Jude Children's Research Hospital
Memphis, TN 38105-2794, USA.
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.
Volume 88,
Issue 2,
pp. 590-598,
07/15/1996
Copyright © 1996 by The American Society of Hematology
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|
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