ウエタ ヨシフミ
  植田 禎史
   所属   医学部 医学科
   職種   助教
論文種別 原著
言語種別 英語
査読の有無 査読あり
表題 HtrA1 serine protease inhibits signaling mediated by Tgfbeta family proteins.
掲載誌名 正式名:Development
略  称:Development
ISSNコード:0950-1991(Print)0950-1991(Linking)
巻・号・頁 131(5),1041-1053頁
著者・共著者 Oka Chio†, Tsujimoto Rumi, Kajikawa Miwa, Koshiba-Takeuchi Kazuko, Ina Junko, Yano Masato, Tsuchiya Akiho, Ueta Yoshifumi, Soma Akinobu, Kanda Hidenobu, Matsumoto Michio, Kawaichi Masashi*
発行年月 2004/03
概要 HtrA1, a member of the mammalian HtrA serine protease family, has a highly conserved protease domain followed by a PDZ domain. Because HtrA1 is a secretory protein and has another functional domain with homology to follistatin, we examined whether HtrA1 functions as an antagonist of Tgfbeta family proteins. During embryo development, mouse HtrA1 was expressed in specific areas where signaling by Tgfbeta family proteins plays important regulatory roles. The GST-pulldown assay showed that HtrA1 binds to a broad range of Tgfbeta family proteins, including Bmp4, Gdf5, Tgfbetas and activin. HtrA1 inhibited signaling by Bmp4, Bmp2, and Tgfbeta1 in C2C12 cells, presumably by preventing receptor activation. Experiments using a series of deletion mutants indicated that the binding activity of HtrA1 required the protease domain and a small linker region preceding it, and that inhibition of Tgfbeta signaling is dependent on the proteolytic activity of HtrA1. Misexpression of HtrA1 near the developing chick eye led to suppression of eye development that was indistinguishable from the effects of noggin. Taken together, these data indicate that HtrA1 protease is a novel inhibitor of Tgfbeta family members.
DOI 10.1242/dev.00999
文献番号 14973287
PMID 14973287