Probing conformational and functional states of human hepatocyte growth factor by a panel of monoclonal antibodies

Masataka Umitsu, Katsuya Sakai, Satoshi Ogasawara, Mika K. Kaneko, Ryoko Asaki, Keiko Tamura-Kawakami, Yukinari Kato, Kunio Matsumoto, Junichi Takagi

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)

Abstract

HGF-Met signaling contributes to various biological events by controlling cell migration. Since the abnormal activation of Met receptor causes cancer progression, inhibitors such as neutralizing antibodies are regarded as promising therapeutics. HGF is secreted as a single-chain (sc) precursor and is processed by extracellular proteases to generate disulfide-bonded two-chain (tc) HGF. Although this proteolytic processing of HGF is necessary for its biological activity, exactly how the proteolysis leads to the conversion of HGF to the active form is still unclar due to the lack of structural information. In order to gain insights about this point, we generated 6 antibodies against HGF. All antibodies recognized different epitopes on the native HGF protein and showed distinct effects when tested in a cell-based HGF-Met signaling assay. They included one antibody (t1E4) that strongly blocks Met activation by tcHGF, as well as one antibody (t8E4) exclusively recognizing the active tcHGF but not inactive scHGF. Thus, a panel of anti-HGF antibodies suitable for probing the structural mechanism of HGF activation were obtained.

Original languageEnglish
Article number33149
JournalScientific reports
Volume6
DOIs
Publication statusPublished - 2016 Sep 9

ASJC Scopus subject areas

  • General

Fingerprint Dive into the research topics of 'Probing conformational and functional states of human hepatocyte growth factor by a panel of monoclonal antibodies'. Together they form a unique fingerprint.

Cite this