Light-Dependent Induction of Early-Response Gene Expression by Calphostin-C

Abstract

Calphostin-C is a compound possessing the ability to inhibit protein kinase C (PKC) by oxidative modification in vitro and to enhance the epidermal growth factor (EGF) receptor phosphorylation in vivo in a light-dependent manner. Here, we found that calphostin-C induced c-fos and c-jun mRNA accumulation in the lung adenocarcinoma cell line A549 in a light-dependent manner. Nuclear run-on assay revealed that this mRNA accumulation took place at the transcription level. However, unlike in vitro, calphostin-C did not inhibit cytosolic PKC activity in vivo, and the gene expression induced by calphostin-C was inhibited by another PKC inhibitor, staurosporine. Thus, it was suggested that calphostin-C activates cytosolic PKC-dependent signaling pathway to the induction of "early-response gene" expression in a light-dependent manner.