CD43-SPECIFIC ACTIVATION OF T-CELLS INDUCES ASSOCIATION OF CD43 TO FYN KINASE

CD43, the most abundant membrane protein of T lymphocytes, is able to initiate signal transduction pathways that lead to Ca2+ mobilization a nd interleukin-2 production, yet the molecular events involved in CD43 's signal transduction pathway are poorly understood. In the present r eport we show that: activation of both purified T lymphocytes and Jurk at cells, through CD43 cross-linking with the anti-CD43 L10 monclonal antibody, induced CD43 association to Fyn kinase, This association is mediated by the Sre Homology 3 (SH3) domain of Fyn, since a glutathion e S-transferase-Fyn SH3 fusion protein was able to precipitate CD43 fr om lysates of CD43-activated T cells. A synthetic peptide containing t he SH3 binding sites of p85, located within the amino acid sequence (3 00)ERQPAPALPPKPPKP(314) was able to inhibit binding of CD43 to Fyn as well as to the glutathione S-transferase-Fyn SH3 fusion protein. We al so provide evidence that upon CD48 cross-linking Fyn is tyrosine-phosp horylated in a time-dependent manner. Our results suggest that CD43 cr oss-linking on the T cell surface induces the interaction between CD43 and Fyn, presumably through the Fyn SH3 domain and a putative SH3 bin ding site in CD43, leading to Fyn tyrosine phosphorylation and signal propagation.