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(Received for publication, September 1, 1995; and in revised form, November 20, 1995)
Evidence from a large body of studies indicates that CD44 is
involved in a number of important biological processes, including
lymphocyte activation and homing, hematopoiesis, and tumor progression
and metastasis. A proper understanding of the role of CD44 in these
processes has been severely hampered by a lack of insight into the mode
in which CD44 communicates with intracellular signal transduction
pathways. In this report, we have addressed this aspect of CD44
functioning by studying CD44 signaling in T lymphocytes. We show that
ligation of CD44 by monoclonal antibodies (mAbs) transduces signals to
T cells which lead to tyrosine phosphorylation of ZAP-70 and other
intracellular proteins. In vitro kinase assays demonstrate
that cross-linking of CD44 induces an increase in the intrinsic
activity of p56. Furthermore,
immunoprecipitations show that CD44 is physically associated with
p56
. Our findings suggest that tyrosine kinases,
particularly p56
, play a central role in CD44
mediated signaling.
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