Human Crossveinless-2 is a novel inhibitor of bone morphogenetic proteins

被引:67
作者
Binnerts, ME [1 ]
Wen, XH [1 ]
Canté-Barrett, K [1 ]
Bright, J [1 ]
Chen, HT [1 ]
Asundi, V [1 ]
Sattari, P [1 ]
Tang, T [1 ]
Boyle, B [1 ]
Funk, W [1 ]
Rupp, F [1 ]
机构
[1] Nuvelo, Sunnyvale, CA 94085 USA
关键词
D O I
10.1016/j.bbrc.2004.01.048
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Drosophila Crossveinless-2 (dCV-2) is required for local activation of Mad phosphorylation in the fruit fly wing and has been postulated to be a positive regulator of BMP-mediated signaling. In contrast, the presence of 5 Chordin-like cysteine-rich domains in the CV-2 protein suggests that CV-2 belongs to a family of well-established inhibitors of BMP function that includes Chordin and Sog [Development 127 (2000) 3947]. We have identified a human homolog of Drosophila CV-2 (hCV-2). Here we show that purified recombinant hCV-2 protein inhibits BMP-2 and BMP-4 dependent osteogenic differentiation of W-20-17 cells, as well as BMP dependent chondrogenic differentiation of ATDC5 cells. Interestingly, hCV-2 messenger RNA is expressed at high levels in human primary chondrocytes, whereas expression in primary human osteoblasts is low. These results suggest that hCV-2 may regulate BMP responsiveness of osteoblasts and chondrocytes in vivo. Taken together we have shown that contrary to the function predicted from the fruit fly, Crossveinless-2 is a novel inhibitor of BMP function. (C) 2004 Elsevier Inc. All rights reserved.
引用
收藏
页码:272 / 280
页数:9
相关论文
共 36 条
[1]   Chordin-like CR domains and the regulation of evolutionarily conserved extracellular signaling systems [J].
Abreu, JG ;
Coffinier, C ;
Larraín, J ;
Oelgeschläger, M ;
De Robertis, EM .
GENE, 2002, 287 (1-2) :39-47
[2]   A CHONDROGENIC CELL-LINE DERIVED FROM A DIFFERENTIATING CULTURE OF AT805 TERATOCARCINOMA CELLS [J].
ATSUMI, T ;
MIWA, Y ;
KIMATA, K ;
IKAWA, Y .
CELL DIFFERENTIATION AND DEVELOPMENT, 1990, 30 (02) :109-116
[3]   The organizer factors Chordin and Noggin are required for mouse forebrain development [J].
Bachiller, D ;
Klingensmith, J ;
Kemp, C ;
Belo, JA ;
Anderson, RM ;
May, SR ;
McMahon, JA ;
McMahon, AP ;
Harland, RM ;
Rossant, J ;
De Robertis, EM .
NATURE, 2000, 403 (6770) :658-661
[4]   Extracellular regulation of BMP signaling in vertebrates: A cocktail of modulators [J].
Balemans, W ;
Van Hul, W .
DEVELOPMENTAL BIOLOGY, 2002, 250 (02) :231-250
[5]  
Bellusci S, 1996, DEVELOPMENT, V122, P1693
[6]   Twisted gastrulation can function as a BMP antagonist [J].
Chang, CB ;
Holtzman, DA ;
Chau, S ;
Chickering, T ;
Woolf, EA ;
Holmgren, LM ;
Bodorova, J ;
Gearing, DP ;
Holmes, WE ;
Brivanlou, AH .
NATURE, 2001, 410 (6827) :483-487
[7]  
Coffinier Catherine, 2002, Gene Expression Patterns, V2, P189, DOI 10.1016/S0925-4773(02)00420-3
[8]  
Conley CA, 2000, DEVELOPMENT, V127, P3947
[9]   Regulation of bone morphogenetic protein activity by pro domains and proprotein convertases [J].
Constam, DB ;
Robertson, EJ .
JOURNAL OF CELL BIOLOGY, 1999, 144 (01) :139-149
[10]  
DUCY P, 1995, MOL CELL BIOL, V15, P1858