ULTRAVIOLET-RADIATION RAPIDLY INDUCES TYROSINE PHOSPHORYLATION AND CALCIUM SIGNALING IN LYMPHOCYTES

UV radiation is known to induce lymphocyte nonresponsiveness both in v itro and in vivo. We have found that UV radiation rapidly induced tyro sine phosphorylation and calcium signaling in normal human peripheral blood lymphocytes, In the leukemic T cell line Jurkat and the Burkitt' s lymphoma cell line Ramos, UV rapidly induced tyrosine phosphorylatio n in a wavelength-dependent manner, giving strong signals after UVB an d UVC, but not UVA, irradiation. Similarly, in Jurkat cells UV-induced calcium signals were dependent on the dose of UVB or UVC irradiation over a range of 150-1200 J/m2, but only a small signal was observed fo r UVA at a dose of 1200 J/m2 . The UV-induced calcium signals were blo cked by the tyrosine kinase inhibitor herbimycin A, indicating that th ey were dependent on tyrosine phosphorylation. Phospholipase C (PLC) g amma1 was tyrosine phosphorylated in response to UV irradiation but to a lesser extent than observed after CD3 cross-linking. However, PLCga mmal-associated proteins demonstrated to bind to the PLCgamma1 SH2 dom ain were tyrosine phosphorylated strongly after UV irradiation. A simi lar dose response was observed for the inhibition by herbimycin A of U V-induced calcium signals and UV-induced tyrosine phosphorylation of P LCgamma1 and associated proteins. We propose that in contrast to CD3/T i stimulation, UV aberrantly triggers lymphocyte signal transduction p athways by a mechanism that bypasses normal receptor control.