Inhibition of calcium signaling in ultraviolet-irradiated fibroblasts: Role of tyrosine phosphorylation and protein kinase C

Our aim was to study whether ultraviolet radiation produced any alterations in the subsequent signaling response of V79 fibroblasts to mitogenic stimu lus. In ultraviolet C (UVC)-irradiated V79 fibroblasts, increase in cytosol ic calcium in response to thrombin was nearly abolished in the presence of 3 mM external Ca2+. UVC-treated V79 cells showed a greatly enhanced permeab ility to Ca2+ which was reversed by pretreatment with genistein, a tyrosine kinase inhibitor. Genistein also alleviated the inhibition of thrombin res ponse caused by WC. In WC-treated cells, significant activation of protein kinase C (PKC) occurred only on exposure to 3 mM external calcium and PKC i nhibitors (H-7 or staurosporine) reversed UVC-induced adverse effects on th e thrombin response. Therefore, it is likely that protein tyrosine phosphor ylation by UVC may play a role in the subsequent inhibition of thrombin res ponse in V79 cells through increased calcium influx and activation of PKC. (C) 1999 Academic Press.