ハギハラ カナコ   Hagihara Kanako
  萩原 加奈子
   所属   兵庫医科大学  薬学部 医療薬学科
   職種   助教
言語種別 英語
発行・発表の年月 2013
形態種別 学術雑誌
査読 査読あり
標題 Fingolimod (FTY720) stimulates Ca(2+)/calcineurin signaling in fission yeast.
執筆形態 共著
掲載誌名 PloS one
掲載区分国外
巻・号・頁 8(12),pp.e81907
著者・共著者 Hagihara Kanako, Kita Ayako, Mizukura Aya, Yao Mariko, Kitai Yuki, Kunoh Tatsuki, Masuko Takashi, Matzno Sumio, Chiba Kenji, Sugiura Reiko
概要 Fingolimod hydrochloride (FTY720) is the first in class of sphingosine 1-phosphate (S1P) receptor modulator approved to treat multiple sclerosis via down-regulation of G protein-coupled S1P receptor 1 by its phosphorylated form (FTY720-P). To gain further insights into molecular mechanisms of FTY720 action, the effect of FTY720 on Ca(2+) signaling in fission yeast was analyzed. The addition of Ca(2+) enhanced the sensitivity induced by FTY720, and mutants lacking genes required for calcium homeostasis, including calcineurin and its downstream transcription factor, Ppb1-responsive zinc finger protein (Prz1), were hypersensitive to FTY720 and CaCl2. Notably, the FTY720-mediated Ca(2+) influx and calcineurin activation were reduced markedly by the deletion of yam8 (+) or cch1 (+) encoding putative subunits of a Ca(2+) channel. These results suggest that the FTY720-stimulated Ca(2+)/calcineurin signaling activation partly involves the Yam8/Cch1 channel in fission yeast.
DOI 10.1371/journal.pone.0081907
ISSN 1932-6203
PMID 24312601