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HGF/NK4 is a specific antagonist for pleiotrophic actions of hepatocyte growth factor
Author(s) -
Date Kazuhiko,
Matsumoto Kunio,
Shimura Hideo,
Tanaka Masao,
Nakamura Toshikazu
Publication year - 1997
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(97)01475-0
Subject(s) - hepatocyte growth factor , kringle domain , chemistry , antagonist , microbiology and biotechnology , medicine , angiogenesis , cancer research , endocrinology , biology , receptor , biochemistry , plasmin , enzyme
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 α‐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.