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

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22 July 2002

journal article
research article
Published by Springer Nature in Nature Cell Biology

Vol. 4 (8) , 599-604
https://doi.org/10.1038/ncb826

Abstract

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 domains^3,4,5,6. 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.

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