title: Human Crossveinless-2 is a novel inhibitor of bone morphogenetic proteins.
abstract: 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.
authors.affiliation: Nuvelo(TM), 675 Almanor Avenue, Sunnyvale, CA 94085, USA. mbinnerts@nuvelo.com
authors.forename: Minke E
authors.initials: ME
authors.lastname: Binnerts
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Wen
authors.forename: Kirsten
authors.initials: K
authors.lastname: Canté-Barrett
authors.forename: Jessica
authors.initials: J
authors.lastname: Bright
authors.forename: Huang-Tsu
authors.initials: HT
authors.lastname: Chen
authors.forename: Vinod
authors.initials: V
authors.lastname: Asundi
authors.forename: Peter
authors.initials: P
authors.lastname: Sattari
authors.forename: Tom
authors.initials: T
authors.lastname: Tang
authors.forename: Bryan
authors.initials: B
authors.lastname: Boyle
authors.forename: Walter
authors.initials: W
authors.lastname: Funk
authors.forename: Fabio
authors.initials: F
authors.lastname: Rupp
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D055396:Bone Morphogenetic Protein 2; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D002454:Cell Differentiation; D002455:Cell Division; D002460:Cell Line; D002478:Cells, Cultured; D003545:Cysteine / Q000737:chemistry; D018076:DNA, Complementary / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004330:Drosophila; D029721:Drosophila Proteins / Q000378:metabolism / Q000502:physiology*; D006023:Glycoproteins / Q000737:chemistry; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000737:chemistry; D051379:Mice; D010006:Osteoblasts / Q000378:metabolism; D010641:Phenotype; D010766:Phosphorylation; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D014018:Tissue Distribution; D016212:Transforming Growth Factor beta
chemical_list: C525718:BMP2 protein, human; C525809:BMP4 protein, human; C525719:Bmp2 protein, mouse; C525810:Bmp4 protein, mouse; D055396:Bone Morphogenetic Protein 2; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins; D018076:DNA, Complementary; D029721:Drosophila Proteins; D006023:Glycoproteins; D036341:Intercellular Signaling Peptides and Proteins; D012333:RNA, Messenger; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; C415644:cv-2 protein, Drosophila; C499469:recombinant human bone morphogenetic protein-2; C091428:sog protein, Drosophila; C054234:chordin; D000469:Alkaline Phosphatase; D003545:Cysteine