The protein product of the proto-oncogene c-cbl forms a complex with
phosphatidylinositol 3-kinase p85 and CD19 in anti-IgM-stimulated human
B-lymphoma cells
M Beckwith, G Jorgensen and DL Longo
Intramural Research Support Program, SAIC/Frederick, Frederick Cancer
Research and Development Center, MD, USA.
Multiple signal transduction cascades, consisting of multiple interacting
proteins, are activated following stimulation through most cell surface
receptors, including the immunoglobulin receptor of B lymphocytes. In this
report, we investigated the multimolecular complexes formed following
anti-Ig stimulation of a human B-lymphoma cell line, resulting in
activation of phosphatidylinositol 3-kinase (PI3K). PI3K is a lipid kinase
that consists of an 85-kD regulatory subunit, bound to a 110-kD catalytic
subunit. CD19 is a 95-kD B-cell surface marker that contains a consensus
binding motif for PI3Kp85 in the cytoplasmic domain and recruits PI3K
activity in activated B cells. The protein product of the c-cbl
protooncogene is a 120-kD protein that is expressed in early B-lineage
cells and in myeloid cells and is phosphorylated on tyrosine following
receptor-mediated signaling in T and B lymphocytes. We demonstrate here
that phosphorylated c-cbl complexes with CD19 and with PI3Kp85 via its
C-terminal SH2 domain, and that both c-cbl and CD19 are associated with
active PI3K in anti-Ig- stimulated cells. Although we cannot differentiate
between a three- component, c-cbl/CD19/p85 complex and individual
two-component complexes, these studies suggest that c-cbl may function as a
docking protein, possibly linking distinct signal transduction pathways.
Volume 88,
Issue 9,
pp. 3502-3507,
11/01/1996
Copyright © 1996 by The American Society of Hematology
