Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
???displayArticle.abstract???
Connective-tissue growth factor (CTGF) is a secreted protein implicated in multiple cellular events including angiogenesis, skeletogenesis and wound healing. It is a member of the CCN family of secreted proteins, named after CTGF, cysteine-rich 61 (CYR61), and nephroblastoma overexpressed (NOV) proteins. The molecular mechanism by which CTGF or other CCN proteins regulate cell signalling is not known. CTGF contains a cysteine-rich domain (CR) similar to those found in chordin and other secreted proteins, which in some cases have been reported to function as bone morphogenetic protein (BMP) and TGF-beta binding domains. Here we show that CTGF directly binds BMP4 and TGF-beta 1 through its CR domain. CTGF can antagonize BMP4 activity by preventing its binding to BMP receptors and has the opposite effect, enhancement of receptor binding, on TGF-beta 1. These results show that CTGF inhibits BMP and activates TGF-beta signals by direct binding in the extracellular space.
Adams,
The thrombospondin type 1 repeat (TSR) superfamily: diverse proteins with related roles in neuronal development.
2000, Pubmed
Adams,
The thrombospondin type 1 repeat (TSR) superfamily: diverse proteins with related roles in neuronal development.
2000,
Pubmed
Bork,
The modular architecture of a new family of growth regulators related to connective tissue growth factor.
1993,
Pubmed
Frazier,
Stimulation of fibroblast cell growth, matrix production, and granulation tissue formation by connective tissue growth factor.
1996,
Pubmed
Garcia Abreu,
Chordin-like CR domains and the regulation of evolutionarily conserved extracellular signaling systems.
2002,
Pubmed
Grotendorst,
A novel transforming growth factor beta response element controls the expression of the connective tissue growth factor gene.
1996,
Pubmed
Holmes,
CTGF and SMADs, maintenance of scleroderma phenotype is independent of SMAD signaling.
2001,
Pubmed
Hunt,
von Willebrand factor shares a distinctive cysteine-rich domain with thrombospondin and procollagen.
1987,
Pubmed
Iemura,
Direct binding of follistatin to a complex of bone-morphogenetic protein and its receptor inhibits ventral and epidermal cell fates in early Xenopus embryo.
1998,
Pubmed
,
Xenbase
Inoki,
Connective tissue growth factor binds vascular endothelial growth factor (VEGF) and inhibits VEGF-induced angiogenesis.
2002,
Pubmed
Katagiri,
The non-osteogenic mouse pluripotent cell line, C3H10T1/2, is induced to differentiate into osteoblastic cells by recombinant human bone morphogenetic protein-2.
1990,
Pubmed
Kim,
Identification of a family of low-affinity insulin-like growth factor binding proteins (IGFBPs): characterization of connective tissue growth factor as a member of the IGFBP superfamily.
1997,
Pubmed
Kireeva,
Cyr61 and Fisp12 are both ECM-associated signaling molecules: activities, metabolism, and localization during development.
1997,
Pubmed
Kothapalli,
Transforming growth factor beta induces anchorage-independent growth of NRK fibroblasts via a connective tissue growth factor-dependent signaling pathway.
1997,
Pubmed
Larraín,
BMP-binding modules in chordin: a model for signalling regulation in the extracellular space.
2000,
Pubmed
,
Xenbase
Larraín,
Proteolytic cleavage of Chordin as a switch for the dual activities of Twisted gastrulation in BMP signaling.
2001,
Pubmed
,
Xenbase
Massagué,
Identification of receptors for type-beta transforming growth factor.
1987,
Pubmed
Masuhara,
Use of monoclonal antibody to detect bone morphogenetic protein-4 (BMP-4).
1995,
Pubmed
Moussad,
Connective tissue growth factor: what's in a name?
2000,
Pubmed
Nakayama,
A novel chordin-like protein inhibitor for bone morphogenetic proteins expressed preferentially in mesenchymal cell lineages.
2001,
Pubmed
,
Xenbase
Pearce,
A mouse cerberus/Dan-related gene family.
1999,
Pubmed
,
Xenbase
Persson,
The L45 loop in type I receptors for TGF-beta family members is a critical determinant in specifying Smad isoform activation.
1998,
Pubmed
,
Xenbase
Piccolo,
Dorsoventral patterning in Xenopus: inhibition of ventral signals by direct binding of chordin to BMP-4.
1996,
Pubmed
,
Xenbase
Roberts,
Transforming growth factor type beta: rapid induction of fibrosis and angiogenesis in vivo and stimulation of collagen formation in vitro.
1986,
Pubmed
Robson,
Inner cell mass-specific expression of a cell adhesion molecule (PECAM-1/CD31) in the mouse blastocyst.
2001,
Pubmed
Sakuta,
Ventroptin: a BMP-4 antagonist expressed in a double-gradient pattern in the retina.
2001,
Pubmed
,
Xenbase
Sasai,
Xenopus chordin: a novel dorsalizing factor activated by organizer-specific homeobox genes.
1994,
Pubmed
,
Xenbase
Segarini,
The low density lipoprotein receptor-related protein/alpha2-macroglobulin receptor is a receptor for connective tissue growth factor.
2001,
Pubmed
Smith,
Expression cloning of noggin, a new dorsalizing factor localized to the Spemann organizer in Xenopus embryos.
1992,
Pubmed
,
Xenbase
Wrana,
TGF beta signals through a heteromeric protein kinase receptor complex.
1992,
Pubmed
Zhu,
Type IIA procollagen containing the cysteine-rich amino propeptide is deposited in the extracellular matrix of prechondrogenic tissue and binds to TGF-beta1 and BMP-2.
1999,
Pubmed
