Erk-independent partial activation of AP-1 sites by the hepatitis B virus HBx protein

F Henkler, AR Lopes, M Jones and R Koshy Imperial College of Science, Technology and Medicine, Hammersmith Campus, Department of Infectious Diseases, London, UK. fhenkle@nimr.mrc.ac.uk The hepatitis B virus X protein (HBx) is suggested to regulate transcription by stimulation of intracellular signalling pathways. We have analysed the effects of HBx on activation of the MAP kinase (Erk) and JNK/SAPK signalling pathways and confirm a stimulation of the Erk/MAP kinase in quiescent cells. However, a substantial Erk- independent activation of AP-1, and phosphorylation of c-Jun (serine- 63), but not Erk-2, was induced by HBx in dividing, serum-maintained cells. These data suggest that HBx promiscuously activates Erk and JNK responsive pathways and that its overall effect on signalling may be influenced by external mitogenic stimuli.