2016
DOI: 10.1038/srep33149
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Probing conformational and functional states of human hepatocyte growth factor by a panel of monoclonal antibodies

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 … Show more

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Cited by 8 publications
(8 citation statements)
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References 27 publications
(34 reference statements)
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“…a6b1 integrin is a major cell surface adhesion receptor for a basement membrane component laminin, and is a critical molecule that supports growth and survival of embryonic stem cells as well as induced pluripotent stem cells during the culture (Miyazaki et al, 2012). Among 24 integrin heterodimers present in mammals (Hynes, 2002), crystal structures are available for Arg-Gly-Asp (RGD)-binding integrins (Dong et al, 2014;Nagae et al, 2012;Van Agthoven et al, 2014;Zhu et al, 2013) and for I-domain-containing integrins (Sen and Springer, 2016;Sen et al, 2013), but laminin-binding integrins that comprise a unique subgroup have escaped structural scrutiny, leading to the lack of molecular understanding of the basement membrane recognition by epithelial cells. Over the last decade, our attempts to crystallize the a6b1 ectodomain by testing more than 20 different construct designs expressed in different host cells, with and without bound Fab fragments from different anti-integrin antibodies including an anti-b1 antibody TS2/16, have all been unsuccessful.…”
Section: Use Of Fv-clasp(v2) In Crystallization Chaperone Applicationsmentioning
confidence: 99%
“…a6b1 integrin is a major cell surface adhesion receptor for a basement membrane component laminin, and is a critical molecule that supports growth and survival of embryonic stem cells as well as induced pluripotent stem cells during the culture (Miyazaki et al, 2012). Among 24 integrin heterodimers present in mammals (Hynes, 2002), crystal structures are available for Arg-Gly-Asp (RGD)-binding integrins (Dong et al, 2014;Nagae et al, 2012;Van Agthoven et al, 2014;Zhu et al, 2013) and for I-domain-containing integrins (Sen and Springer, 2016;Sen et al, 2013), but laminin-binding integrins that comprise a unique subgroup have escaped structural scrutiny, leading to the lack of molecular understanding of the basement membrane recognition by epithelial cells. Over the last decade, our attempts to crystallize the a6b1 ectodomain by testing more than 20 different construct designs expressed in different host cells, with and without bound Fab fragments from different anti-integrin antibodies including an anti-b1 antibody TS2/16, have all been unsuccessful.…”
Section: Use Of Fv-clasp(v2) In Crystallization Chaperone Applicationsmentioning
confidence: 99%
“…Because the stomach is a typical organ composed of epithelial and mesenchymal cells, and stem cells play important roles in development and regeneration [25], analyses of the localization of sc/tcHGF and its association with MET activation in the stomach may provide a better understanding of how the HGF–MET pathway participates in development, regeneration, and the stem cell behavior of endoderm-derived organs. In a recent study, we obtained several anti-HGF monoclonal antibodies that recognize different epitopes of human HGF [26], one of which selectively recognizes human tcHGF. In this study, we thus investigated the localization of tcHGF and active MET in the developing and regenerating stomach, employing human tcHGF-specific monoclonal antibody and human HGF-knock-in mice.…”
Section: Introductionmentioning
confidence: 99%
“…The clones had heterogeneous HCDR3 in the aspect of sequence length and amino acid composition. Considering the heterogeneity, the clones are expected to bind to different epitopes of hHGF, as reported before 32 .…”
Section: Discussionmentioning
confidence: 77%