Connective-tissue growth factor modulates WNT signalling and interacts with the WNT receptor complex

Sara Mercurio, Branko Latinkic, Nobue Itasaki, Robb Krumlauf, J C Smith

Research output: Contribution to journalArticle (Academic Journal)peer-review

160 Citations (Scopus)
272 Downloads (Pure)

Abstract

Connective-tissue growth factor (CTGF) is a member of the CCN family of secreted proteins. CCN family members contain four characteristic domains and exhibit multiple activities: they associate with the extracellular matrix, they can mediate cell adhesion, cell migration and chemotaxis, and they can modulate the activities of peptide growth factors. Many of the effects of CTGF are thought to be mediated by binding to integrins, whereas others may be because of its recently identified ability to interact with BMP4 and TGF beta. We demonstrate, using Xenopus embryos, that CTGF also regulates signalling through the Wnt pathway, in accord with its ability to bind to the Wnt co-receptor LDL receptor-related protein 6 (LRP6). This interaction is likely to occur through the C-terminal (CT) domain of CTGF, which is distinct from the BMP- and TGF beta-interacting domain. Our results define new activities of CTGF and add to the variety of routes through which cells regulate growth factor activity in development, disease and tissue homeostasis.

Original languageEnglish
Pages (from-to)2137-2147
Number of pages11
JournalDevelopment (Cambridge)
Volume131
Issue number9
Early online date22 Apr 2004
DOIs
Publication statusPublished - May 2004

Keywords

  • Amino Acid Sequence
  • Animals
  • Connective Tissue Growth Factor
  • Embryonic Induction
  • Gene Expression Regulation, Developmental
  • Genes, Reporter
  • Immediate-Early Proteins
  • Intercellular Signaling Peptides and Proteins
  • Low Density Lipoprotein Receptor-Related Protein-6
  • Macromolecular Substances
  • Molecular Sequence Data
  • Morphogenesis
  • Oligonucleotides, Antisense
  • Proto-Oncogene Proteins
  • Receptors, LDL
  • Sequence Alignment
  • Signal Transduction
  • Wnt Proteins
  • Xenopus Proteins
  • Xenopus laevis
  • Zebrafish Proteins

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