ZAP-70 TYROSINE KINASE, CD45, AND T-CELL RECEPTOR INVOLVEMENT IN UV-INDUCED AND H2O2-INDUCED T-CELL SIGNAL-TRANSDUCTION

Several mammalian responses to UV irradiation, including the activatio n of NF-kappa B, are believed to involve tyrosine phosphorylation. UV irradiation and H2O2 treatment of T lymphocytes induce protein tyrosin e phosphorylation and Ca2+ signals similar to those observed following biological stimulation. We have examined the role of cell surface mol ecules in these responses. Normal T lymphocytes whose surface expressi on of CD3 was depleted showed impaired UV-induced tyrosine phosphoryla tion and Ca2+ signals. Similarly, Jurkat T cell lines deficient in CD3 or CD45 expression also gave impaired UV responses. However, all thes e cell types still gave strong Ca2+ and tyrosine phosphorylation respo nses to H2O2. The T cell tyrosine kinase ZAP-70 was found to be highly responsive to UV and H2O2 treatment. ZAP-70 responsiveness to UV requ ired expression of both CD3 and CD45, whereas only CD3 was required fo r the response to H2O2. UV-induced activation of NF-kappa B was blocke d by CD3 depletion, indicating the importance of such cell surface mol ecules in biological responses to UV. In non-lymphoid cells, the epide rmal growth factor receptor displayed increased tyrosine phosphorylati on within seconds of UV irradiation. These results suggest that UV-ind uced signal transduction is mediated via cell surface receptors that n ormally respond to biological stimulation, whereas H2O2 is able to par tially bypass this requirement.