First published online February 18, 2004
Development 131, 502e (2004)
© The Company of Biologists Limited
HtrA1: a novel TGFß antagonist
HtrA1 is a member of the HtrA serine protease family, which is found
ubiquitously in microbes, plants and animals. In humans, HtrA1 is upregulated
in articular chondrocytes during arteroarthritis and is a tumour suppressor
gene that is downregulated in highly invasive tumours. Homology between the
N-terminal region of HtrA1 and follistatin (a Tgfß antagonist) prompted
Oka and co-workers (p.
1041) to examine whether HtrA1 contributes to these diseases by
inhibiting Tgfß signalling. They found that HtrA1 binds to a broad range
of Tgfß family proteins. Furthermore, HtrA1 expression correlates with
Tgfß activity during mouse development, and misexpression of HtrA1 near
to the chick eye suppresses eye development. Surprisingly, however, the
inhibition of Tgfß signalling by HtrA1 requires HtrA1 proteolytic
activity, leading the researchers to propose that the binding of HtrA1 to
Tgfß may not itself inhibit Tgfß, but may help degrade component(s)
of Tgfß signaling by bringing HtrA1 close to its substrate.
Related articles in Development:
- HtrA1 serine protease inhibits signaling mediated by Tgfß family proteins
- Chio Oka, Rumi Tsujimoto, Miwa Kajikawa, Kazuko Koshiba-Takeuchi, Junko Ina, Masato Yano, Akiho Tsuchiya, Yoshihumi Ueta, Akinobu Soma, Hidenobu Kanda, Michio Matsumoto, and Masashi Kawaichi
Development 2004 131: 1041-1053.
[Abstract]
[Full Text]
