HGF NK4 IS A SPECIFIC ANTAGONIST FOR PLEIOTROPIC ACTIONS OF HEPATOCYTE GROWTH-FACTOR/

We prepared a specific antagonist for hepatocyte growth factor (HGF) a nd designated it HGF/NK4. HGF/NK4 is composed of N-terminal 447 amino acids of the alpha-chain of HGF, thus contains the N-terminal hairpin domain and subsequent four kringle domains, HGF/NK4 competitively inhi bited the specific binding of HGF to the receptor, Importantly, HGF/NK 4 neither stimulated DIVA synthesis of primary cultured rat hepatocyte s (mitogenesis) nor induced cell scattering (motogenesis) and branchin g tubulogenesis (morphogenesis) of MDCK renal epithelial cells, howeve r, HGF/NK4 almost completely inhibited the mitogenic, motogenic, and m orphogenic activities of HGF. HGF/NK4 also suppressed tyrosine phospho rylation of the c-Met/HGF receptor induced by HGF, Apparently this is the first documentation of a specific antagonist which abrogates the m itogenic, motogenic, and morphogenic activities of HGF. (C) 1997 Feder ation of European Biochemical Societies.