title: Vertebrate crossveinless 2 is secreted and acts as an extracellular modulator of the BMP signaling cascade.
abstract: In vertebrates and invertebrates, BMP/Dpp (Bone Morphogenetic Protein/Decapentaplegic) signaling regulates the orchestrated processes of embryogenesis. Recent studies have revealed that BMP/Dpp signaling is controlled extracellularly as well as intracellularly. One extracellular regulatory molecule is the Chordin/Short gastrulation protein (Chordin/Sog), a secreted protein that acts as an antagonist to BMP/Dpp. Chordin/Sog contains four cysteine-rich (CR) domains that bind to and inactivate BMP/Dpp. In contrast, a positive regulator has been identified in Drosophila. Named crossveinless 2 (cv-2), this molecule contains five CR domains at the N-terminal half and a von Willebrand factor D domain at the C-terminal part. Genetic data suggest that Cv-2 potentiates Dpp signaling. We isolated chick and mouse CV-2 genes and found that CV-2 is secreted and enhances BMP signaling. Expression patterns were closely related to those of BMPs, supporting the likelihood of a tight link. Our data show for the first time that CV-2 is a conserved, positive regulator of BMP signaling and that CR domain proteins act as both positive and negative modulators of BMP signaling.
authors.affiliation: Institute of Development, Aging, and Cancer, Tohoku University, Aoba, Sendai, Miyagi, Japan.
authors.forename: Mika
authors.initials: M
authors.lastname: Kamimura
authors.forename: Ken
authors.initials: K
authors.lastname: Matsumoto
authors.forename: Kazuko
authors.initials: K
authors.lastname: Koshiba-Takeuchi
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Ogura
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000378:metabolism*; D002642:Chick Embryo; D017124:Conserved Sequence; D003545:Cysteine / Q000737:chemistry; D029721:Drosophila Proteins / Q000737:chemistry / Q000378:metabolism*; D047108:Embryonic Development; D006023:Glycoproteins / Q000737:chemistry / Q000378:metabolism; D057927:Hydrophobic and Hydrophilic Interactions; D019476:Insect Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D036341:Intercellular Signaling Peptides and Proteins / Q000737:chemistry / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction / Q000235:genetics; D014714:Vertebrates / Q000196:embryology*; D014841:von Willebrand Factor / Q000737:chemistry
chemical_list: D019485:Bone Morphogenetic Proteins; D029721:Drosophila Proteins; D006023:Glycoproteins; D019476:Insect Proteins; D036341:Intercellular Signaling Peptides and Proteins; C415644:cv-2 protein, Drosophila; D014841:von Willebrand Factor; C054234:chordin; D003545:Cysteine