Protein Kinase C Activity Is Required for Aryl Hydrocarbon Receptor Pathway-Mediated Signal Transduction

The role of protein kinase C (PKC) in the human aryl hydrocar-bon receptor (hAhR) signal transduction pathway was exam-ined in cell lines stably transfected with pGUDLUC6.1, in which luc1 is solely controlled by four dioxin-responsive elements (DREs). These cell lines, P5A11 and HG40/6, were derived from HeLa and HepG2 cells respectively. Simultaneous treatment of these cells with 2,3,7,8,-tetrachlorodibenzo-p-dioxin (TCDD) and phorbol-12-myristate-13-acetate (PMA) enhanced trans-activation of the reporter construct several-fold relative to cells treated with TCDD alone. PKC inhibitors block the PMA effect and hAhR-mediated signal transduction, demonstrating these processes require PKC activity. Examination of other indepen-dently generated, HeLa-derived cell lines stably transfected with pGUDLUC6.1 demonstrates the PMA effect in P5A11 cell