Connective-tissue growth factor modulates WNT signalling and interacts with the WNT receptor complex.
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.
Mercurio
Sara
S
Division of Developmental Biology, National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK.
Latinkic
Branko
B
Itasaki
Nobue
N
Krumlauf
Robb
R
Smith
J C
JC
D000595:Amino Acid Sequence; D000818:Animals; D055513:Connective Tissue Growth Factor; D004627:Embryonic Induction; D018507:Gene Expression Regulation, Developmental; D017930:Genes, Reporter; D017874:Immediate-Early Proteins / Q000235:genetics / Q000378:metabolism*; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D060488:Low Density Lipoprotein Receptor-Related Protein-6; D046911:Macromolecular Substances; D008969:Molecular Sequence Data; D009024:Morphogenesis / Q000502:physiology; D016376:Oligonucleotides, Antisense / Q000235:genetics / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D011973:Receptors, LDL / Q000235:genetics / Q000378:metabolism*; D016415:Sequence Alignment; D015398:Signal Transduction / Q000502:physiology*; D051153:Wnt Proteins; D029867:Xenopus Proteins / Q000235:genetics / Q000378:metabolism; D014982:Xenopus laevis / Q000033:anatomy & histology / Q000196:embryology; D029961:Zebrafish Proteins
D017874:Immediate-Early Proteins; D036341:Intercellular Signaling Peptides and Proteins; D060488:Low Density Lipoprotein Receptor-Related Protein-6; D046911:Macromolecular Substances; D016376:Oligonucleotides, Antisense; D011518:Proto-Oncogene Proteins; D011973:Receptors, LDL; D051153:Wnt Proteins; D029867:Xenopus Proteins; D029961:Zebrafish Proteins; D055513:Connective Tissue Growth Factor