Connective-tissue growth factor (ctgf) modulates cell signalling by bmp and TGF-β

José G. Abreu, Nan I. Ketpura, Bruno Reversade, E. M. De Robertis

Research output: Contribution to journalArticlepeer-review

769 Scopus citations


Connective-tissue growth factor (CTGF) is a secreted protein implicated in multiple cellular events including angiogenesis, skeletogenesis and wound healing1. 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 proteins2, which in some cases have been reported to function as bone morphogenetic protein (BMP) and TGF-β binding domains3-6. Here we show that CTGF directly binds BMP4 and TGF-β1 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-β1. These results show that CTGF inhibits BMP and activates TGF-β signals by direct binding in the extracellular space.
Original languageEnglish (US)
Pages (from-to)599-604
Number of pages6
JournalNature Cell Biology
Issue number8
StatePublished - Jan 1 2002
Externally publishedYes

ASJC Scopus subject areas

  • Cell Biology


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