T-CELL ACTIVATION THROUGH THE CD43 MOLECULE LEADS TO VAV TYROSINE PHOSPHORYLATION AND MITOGEN-ACTIVATED PROTEIN-KINASE PATHWAY ACTIVATION

CD43, the most abundant membrane protein of T lymphocytes, is able to initiate signals that lead to Ca2+ mobilization and interleukin-a prod uction yet the molecular events involved in signal transduction pathwa y of the CD43 molecule are only beginning to be understood. We have sh own recently that cross-linking CD43 on the cell surface of human T ly mphocytes with the anti-CD43 monoclonal antibody L10 leads to CD43-Fyn kinase interactions and to Fyn phosphorylation on tyrosine residues. This interaction seems to be mediated by the SH3 domain of Fyn and a p roline-rich sequence located in the cytoplasmic domain of CD43. Here w e show that CD43-specific activation of human T lymphocytes induced ty rosine phosphorylation of the adaptor protein Shc and of the guanine e xchange factor Vav, as well as the formation of a macromolecular compl ex that comprises She, GRB2, and Vav. CD43 Ligation resulted in enhanc ed formation of Vav-SLP-76 complexes and in the activation and nuclear translocation of ERK2. Crosslinking of the CD43 molecule in 3T3-CD43( +) cells induced luciferase activity from a construct under the contro l of the Fos serum responsive element, Altogether, these data suggest that the mitogen-activated protein kinase pathway is involved in CD43- dependent interleukin-2 gene expression.