TRANSCRIPTIONAL INDUCTION OF THE AGP EBP (C/EBP-BETA) GENE BY HEPATOCYTE GROWTH-FACTOR/

Hepatocyte growth factor (HGF) is a pleiotropic factor with mitogenic, morphogenic, motogenic, cytotoxic, or growth inhibitory activity, Alt hough the signaling of HGF is mediated through the cell membrane recep tor c-Met, the molecular mechanism of downstream signal transduction r emains obscure, In this report, we present evidence that shows HGF can stimulate the expression of AGP/EBP (C/EB beta P) and NF-kappa B, whi ch are both key transcription factors responsible for the regulation o f many genes under stress conditions or during the acute-phase respons e, Biochemical and functional analysis indicates that the HGF-responsi ve element is located in the region -376 to -352 (URE1) of the 5'-upst ream regulatory sequence of agp/ebp, Activation of NF-kappa B by HGF w as observed to precede the induction of agp/ebp, Further studies indic ate that NF-kappa B can cooperate with AGP/EBP or other members of the C/EBP family to activate the agp/ebp gene in both URE1 and URE2-depen dent manner, These results suggest that the induction of the agp/ebp g ene by HGF is mediated at least in part by its activation of NF-kappa B. The activated NF-kappa B then interacts with AGP/EBP, resulting in the induction of agp/ebp.