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PMID: 12134160 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Connective-tissue growth factor (CTGF) modulates cell signalling by BMP and TGF-beta.

Nature cell biology ·Vol. 4 ·No. 8 ·2002-08-00 ·Pages 599-604

Abreu JG, Ketpura NI, Reversade B, De Robertis EM

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.

MeSH Terms
Amino Acid Sequence Animals Base Sequence Binding Sites Bone Morphogenetic Protein 4 Bone Morphogenetic Proteins/metabolism Connective Tissue Growth Factor DNA, Complementary/genetics Growth Substances/chemistry,genetics,metabolism Immediate-Early Proteins/chemistry,genetics,metabolism Intercellular Signaling Peptides and Proteins Molecular Sequence Data Phenotype Protein Structure, Tertiary RNA, Messenger/genetics,metabolism Sequence Homology, Amino Acid Signal Transduction Transforming Growth Factor beta/metabolism Transforming Growth Factor beta1 Xenopus/embryology,genetics,metabolism Xenopus Proteins
Chemicals
Bone Morphogenetic Protein 4 Bone Morphogenetic Proteins DNA, Complementary Growth Substances Immediate-Early Proteins Intercellular Signaling Peptides and Proteins RNA, Messenger Transforming Growth Factor beta Transforming Growth Factor beta1 Xenopus Proteins bmp4 protein, Xenopus Connective Tissue Growth Factor
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Abreu José G
Howard Hughes Medical Institute and Department of Biological Chemistry, University of California, Riverside, 9095-1662, USA.
Ketpura Nan I
Reversade Bruno
De Robertis E M
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Article Info
Journal
Nature cell biology
Abbr.
Nat Cell Biol
ISSN
1465-7392
DOI
10.1038/ncb826
Published
2002-08-00
Pages
599-604
Language
English
Region
England
NLM ID
100890575
PMCID
PMC2387275
Subset
IM
Grants
NICHD NIH HHS · R37 HD021502 · United States
NICHD NIH HHS · R37 HD021502-16 · United States
NICHD NIH HHS · R37 HD21502-16 · United States
External Links
PubMed source DOI: 10.1038/ncb826 PMC Full Text View journal details
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