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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Sequence
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Animals
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Base Sequence
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Binding Sites
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Bone Morphogenetic Protein 4
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Bone Morphogenetic Proteins / metabolism*
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Connective Tissue Growth Factor
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DNA, Complementary / genetics
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Growth Substances / chemistry
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Growth Substances / genetics
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Growth Substances / metabolism*
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Immediate-Early Proteins / chemistry
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Immediate-Early Proteins / genetics
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Immediate-Early Proteins / metabolism*
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Intercellular Signaling Peptides and Proteins*
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Molecular Sequence Data
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Phenotype
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Protein Structure, Tertiary
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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Sequence Homology, Amino Acid
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Signal Transduction
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Transforming Growth Factor beta / metabolism*
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Transforming Growth Factor beta1
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Xenopus / embryology
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Xenopus / genetics
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Xenopus / metabolism
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Xenopus Proteins
Substances
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Bone Morphogenetic Protein 4
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Bone Morphogenetic Proteins
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DNA, Complementary
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Growth Substances
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Immediate-Early Proteins
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Intercellular Signaling Peptides and Proteins
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RNA, Messenger
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Transforming Growth Factor beta
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Transforming Growth Factor beta1
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Xenopus Proteins
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bmp4 protein, Xenopus
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Connective Tissue Growth Factor