SIGNALING THROUGH CD44 IS MEDIATED BY TYROSINE KINASES - ASSOCIATION WITH P56(LCK) IN T-LYMPHOCYTES

Evidence from a large body of studies indicates that CD44 is involved in a number of important biological processes, including lymphocyte ac tivation and homing, hematopoiesis, and tumor progression and metastas is. 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 CD4 4 communicates with intracellular signal transduction pathways. In thi s report, we have addressed this aspect of CD44 functioning by studyin g CD44 signaling in T lymphocytes. We show that ligation of CD44 by mo noclonal 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(lck). Furthermore, immuno precipitations show that CD44 is physically associated with p56(lck). Our findings suggest that tyrosine kinases, particularly p56(lck), pla y a central role in CD44 mediated signaling.