IDENTIFICATION OF A SIGNALING COMPLEX INVOLVING CD2, ZETA-CHAIN AND P59(FYN) IN T-LYMPHOCYTES

CD2 is a cell surface receptor molecule which has been implicated in c ell-cell adhesion and signaling functions in T lymphocytes and natural killer cells. The mechanism by which extracellular stimuli induce CD2 -regulated signal transduction events is largely unknown. However, the re is increasing evidence that in cells of hematopoietic origin severa l receptor-mediated signaling mechanisms involve transmembrane polypep tides related to the CD3 xi chain and the activation of protein tyrosi ne kinases. We have therefore investigated the potential involvement o f xi chain and src family protein tyrosine kinases in signal transduct ion pathways initiated by CD2. Using in vitro kinase assays on CD2 imm unoprecipitates from detergent lysates of T lymphocytes, we identified a complex consisting of CD2, xi chain and the src family kinases p59( fyn) and p56(lck). Furthermore, using double indirect immunofluorescen ce combined with capping techniques, we have revealed such complexes i n viable T lymphocytes. These findings provide evidence for a multimol ecular signaling complex consisting of at least CD2, xi chain and p59( fyn) in T lymphocytes and suggest a critical role for this complex in the initiation of CD2-mediated cellular activation by regulating the a ctivation of intracellular signaling molecules.