TNFα promotes ET-1 production by activating the IKK complex, which, in turn, activates ERK and JNK via their direct phosphorylation; phosphorylated JNK translocates to the nucleus to activate c-Jun, which binds to the preproET-1 promoter and triggers preproET-1 mRNA and protein expression. The transcription factor (or factors) which is (are) activated by ERK to stimulate preproET-1 mRNA and protein expression remain(s) unknown. Abbreviations: TF = transcription factor, Co-A = co-activator