Identification of a signaling complex involving CD2, zeta chain and p59fyn in T lymphocytes

CD2 is a cell surface receptor molecule which has been implicated in cell-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, there is increasing evidence that in cells of hematopoietic origin several receptor-mediated signaling mechanisms involve transmembrane polypeptides related to the CD3 zeta chain and the activation of protein tyrosine kinases. We have therefore investigated the potential involvement of zeta chain and src family protein tyrosine kinases in signal transduction pathways initiated by CD2. Using in vitro kinase assays on CD2 immunoprecipitates from detergent lysates of T lymphocytes, we identified a complex consisting of CD2, zeta chain and the src family kinases p59fyn and p56lck. Furthermore, using double indirect immunofluorescence combined with capping techniques, we have revealed such complexes in viable T lymphocytes. These findings provide evidence for a multimolecular signaling complex consisting of at least CD2, zeta chain and p59fyn in T lymphocytes and suggest a critical role for this complex in the initiation of CD2-mediated cellular activation by regulating the activation of intracellular signaling molecules.