Yoshifumi Ueta    Department   School of Medicine, School of Medicine    Position   Assistant Professor
Article types	Original article
Language	English
Peer review	Peer reviewed
Title	HtrA1 serine protease inhibits signaling mediated by Tgfbeta family proteins.
Journal	Formal name：Development Abbreviation：Development ISSN code：0950-1991(Print)0950-1991(Linking)
Volume, Issue, Page	131(5),pp.1041-1053
Author and coauthor	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*
Publication date	2004/03
Summary	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
Document No.	14973287
PMID	14973287