title: HGF/NK4 is a specific antagonist for pleiotrophic actions of hepatocyte growth factor.
abstract: We prepared a specific antagonist for hepatocyte growth factor (HGF) and 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 inhibited the specific binding of HGF to the receptor. Importantly, HGF/NK4 neither stimulated DNA synthesis of primary cultured rat hepatocytes (mitogenesis) nor induced cell scattering (motogenesis) and branching tubulogenesis (morphogenesis) of MDCK renal epithelial cells, however, HGF/NK4 almost completely inhibited the mitogenic, motogenic, and morphogenic activities of HGF. HGF/NK4 also suppressed tyrosine phosphorylation of the c-Met/HGF receptor induced by HGF. Apparently this is the first documentation of a specific antagonist which abrogates the mitogenic, motogenic, and morphogenic activities of HGF.
authors.affiliation: Division of Biochemistry, Biomedical Research Center, Osaka University Medical School, Suita, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Date
authors.forename: K
authors.initials: K
authors.lastname: Matsumoto
authors.forename: H
authors.initials: H
authors.lastname: Shimura
authors.forename: M
authors.initials: M
authors.lastname: Tanaka
authors.forename: T
authors.initials: T
authors.lastname: Nakamura
mesh_terms: D000818:Animals; D001667:Binding, Competitive; D002465:Cell Movement; D048429:Cell Size; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis; D004285:Dogs; D017228:Hepatocyte Growth Factor / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D007668:Kidney / Q000166:cytology; D018082:Kringles; D008099:Liver / Q000166:cytology; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D010766:Phosphorylation; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism; D051381:Rats; D011994:Recombinant Proteins; D017421:Sequence Analysis; D013329:Structure-Activity Relationship; D014443:Tyrosine / Q000378:metabolism
chemical_list: D010446:Peptide Fragments; D011994:Recombinant Proteins; D014443:Tyrosine; D017228:Hepatocyte Growth Factor; D004247:DNA; D019859:Proto-Oncogene Proteins c-met