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Kitazawa, Takafumi; Ikeda, Yoichi*; Sakakibara, Toshiro*; Matsuo, Akira*; Shimizu, Yusei*; Tokunaga, Yo; Haga, Yoshinori; Kindo, Koichi*; Nambu, Yusuke*; Ikeuchi, Kazuhiko*; et al.
Physical Review B, 108(8), p.085105_1 - 085105_7, 2023/08
Yamazaki, Yuji*; Tamada, Taro; Kasai, Noriyuki*; Urakawa, Itaru*; Aono, Yukiko*; Hasegewa, Hisashi*; Fujita, Toshiro*; Kuroki, Ryota; Yamashita, Takeyoshi*; Fukumoto, Seiji*; et al.
Journal of Bone and Mineral Research, 23(9), p.1509 - 1518, 2008/09
Times Cited Count:150 Percentile:94.53Fibroblast growth factor (FGF)23 is proposed to play a physiological role in the regulation of phosphate and vitamin D metabolism; deranged circulatory levels of FGF23 cause several diseases with abnormal mineral metabolism. We developed two antibodies (FN1 and FC1) that recognize the N- and C-terminal regions of FGF23, respectively. Both FN1 and FC1 inhibited FGF23 activity in a cell-based Klotho-dependent reporter assay. The present study using neutralizing antibodies confirms that FGF23 is a physiological regulator of phosphate and vitamin D metabolism. Then, we addressed the mechanism of action for these neutralizing antibodies. Structural analysis of the FGF23/FN1-Fab complex revealed that FN1 masked putative FGF receptor-binding sites in the N-terminal domain of FGF23, while biochemical analyses showed that FC1 interfered with the association between FGF23 and Klotho by binding to the C-terminal domain of FGF23. Taken together, our results suggest that the N- and C-terminal domains of FGF23 are responsible for association with cognate FGF receptors and Klotho, respectively, and that these interactions are indispensable for FGF23 activity.
Mori, Masahiro; Ishida, Shinichi; Ando, Toshiro; ; Asakura, Nobuyuki; Azumi, Masafumi; A.A.E.van-Blokland*; G.J.Frieling*; Fujii, Tsuneyuki; Fujita, Takaaki; et al.
Nuclear Fusion, 34(7), p.1045 - 1053, 1994/00
Times Cited Count:32 Percentile:80(Physics, Fluids & Plasmas)no abstracts in English
Fujita, Ichiro*; Amemiya, Susumu*; Hino, Tomoaki*; Yamashina, Toshiro*; Akiba, Masato; Ando, Toshiro; Seki, Masahiro
Journal of Nuclear Materials, 196-198, p.168 - 173, 1992/12
Times Cited Count:7 Percentile:57.46(Materials Science, Multidisciplinary)no abstracts in English