|
|
|
|
|
|
|
||||
| Home Help Feedback Subscriptions Archive Search Table of Contents | ||||
First published online February 18, 2004
doi: 10.1242/10.1242/dev.00999
1 Division of Gene Function in Animals, Nara Institute of Science and
Technology, 8916-5 Takayama, Ikoma, Nara 630-0101, Japan
2 Division of Metabolic Regulation of Animal Cells, Nara Institute of Science
and Technology, 8916-5 Takayama, Ikoma, Nara 630-0101, Japan
* Author for correspondence (e-mail: mkawaich{at}bs.aist-nara.ac.jp)
Accepted 21 November 2003
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 Tgfß family proteins. During embryo development, mouse HtrA1 was expressed in specific areas where signaling by Tgfß family proteins plays important regulatory roles. The GST-pulldown assay showed that HtrA1 binds to a broad range of Tgfß family proteins, including Bmp4, Gdf5, Tgfßs and activin. HtrA1 inhibited signaling by Bmp4, Bmp2, and Tgfß1 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 Tgfß 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 Tgfß family members.
Key words: HtrA1, Tgfß, Bmp, Serine protease, Noggin, Follistatin
Related articles in Development:
This article has been cited by other articles:
|
|
 |
|
  A. Gaultier, S. Arandjelovic, S. Niessen, C. D. Overton, M. F. Linton, S. Fazio, W. M. Campana, B. F. Cravatt III, and S. L. Gonias Regulation of tumor necrosis factor receptor-1 and the IKK-NF-{kappa}B pathway by LDL receptor-related protein explains the antiinflammatory activity of this receptor Blood, June 1, 2008; 111(11): 5316 - 5325. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. D. Hadfield, C. F. Rock, C. A. Inkson, S. L. Dallas, L. Sudre, G. A. Wallis, R. P. Boot-Handford, and A. E. Canfield HtrA1 Inhibits Mineral Deposition by Osteoblasts: REQUIREMENT FOR THE PROTEASE AND PDZ DOMAINS J. Biol. Chem., February 29, 2008; 283(9): 5928 - 5938. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Mitko, S. E Ulbrich, H. Wenigerkind, F. Sinowatz, H. Blum, E. Wolf, and S. Bauersachs Dynamic changes in messenger RNA profiles of bovine endometrium during the oestrous cycle Reproduction, February 1, 2008; 135(2): 225 - 240. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. T. Runyon, Y. Zhang, B. A. Appleton, S. L. Sazinsky, P. Wu, B. Pan, C. Wiesmann, N. J. Skelton, and S. S. Sidhu Structural and functional analysis of the PDZ domains of human HtrA1 and HtrA3 Protein Sci., November 1, 2007; 16(11): 2454 - 2471. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Watanabe, M. Shionyu, T. Kimura, K. Kimata, and H. Watanabe Splicing Factor 3b Subunit 4 Binds BMPR-IA and Inhibits Osteochondral Cell Differentiation J. Biol. Chem., July 13, 2007; 282(28): 20728 - 20738. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Z. Yang, N. J. Camp, H. Sun, Z. Tong, D. Gibbs, D. J. Cameron, H. Chen, Y. Zhao, E. Pearson, X. Li, et al. A Variant of the HTRA1 Gene Increases Susceptibility to Age-Related Macular Degeneration Science, November 10, 2006; 314(5801): 992 - 993. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Zupkovitz, J. Tischler, M. Posch, I. Sadzak, K. Ramsauer, G. Egger, R. Grausenburger, N. Schweifer, S. Chiocca, T. Decker, et al. Negative and Positive Regulation of Gene Expression by Mouse Histone Deacetylase 1 Mol. Cell. Biol., November 1, 2006; 26(21): 7913 - 7928. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. R. Bowers, J. W. Kim, T. C. Otto, and M. D. Lane Stable stem cell commitment to the adipocyte lineage by inhibition of DNA methylation: Role of the BMP-4 gene PNAS, August 29, 2006; 103(35): 13022 - 13027. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. H. Vesper, L. T. Raetzman, and S. A. Camper Role of Prophet of Pit1 (PROP1) in Gonadotrope Differentiation and Puberty Endocrinology, April 1, 2006; 147(4): 1654 - 1663. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Nie, Y. Li, K. Hale, H. Okada, U. Manuelpillai, E. M. Wallace, and L. A. Salamonsen Serine Peptidase HTRA3 Is Closely Associated with Human Placental Development and Is Elevated in Pregnancy Serum Biol Reprod, February 1, 2006; 74(2): 366 - 374. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Naitoh, H. Kubota, M. Ikeda, T. Tanaka, H. Shirane, S. Suzuki, and K. Nagata Gene expression in human keloids is altered from dermal to chondrocytic and osteogenic lineage Genes Cells, November 1, 2005; 10(11): 1081 - 1091. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. De Luca, M. De Falco, L. De Luca, R. Penta, V. Shridhar, F. Baldi, M. Campioni, M. G. Paggi, and A. Baldi Pattern of Expression of HtrA1 During Mouse Development J. Histochem. Cytochem., December 1, 2004; 52(12): 1609 - 1617. [Abstract] [Full Text] [PDF]
|
|
