CCN2/CTGF binds to fibroblast growth factor receptor 2 and modulates its signaling

FEBS Lett. 2012 Dec 14;586(24):4270-5. doi: 10.1016/j.febslet.2012.10.038. Epub 2012 Nov 6.

Abstract

CCN2 plays a critical role in the development of mesenchymal tissues such as cartilage and bone, and the binding of CCN2 to various cytokines and receptors regulates their signaling.By screening a protein array, we found that CCN2 could bind to fibroblast growth factor receptors (FGFRs) 2 and 3, with a higher affinity toward FGFR2.We ascertained that FGFR2 bound to CCN2 and that the binding of FGFR2 to FGF2 and FGF4 was enhanced by CCN2.CCN2 and FGF2 had a collaborative effect on the phosphorylation of ERK and the differentiation of osteoblastic cells.The present results indicate the biological significance of the binding of CCN2 to FGFR2 in bone metabolism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Chondrocytes / metabolism
  • Connective Tissue Growth Factor / chemistry
  • Connective Tissue Growth Factor / metabolism*
  • Connective Tissue Growth Factor / pharmacology
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Fibroblast Growth Factor 2 / chemistry
  • Fibroblast Growth Factor 2 / metabolism
  • Fibroblast Growth Factor 2 / pharmacology
  • Fibroblast Growth Factor 4 / chemistry
  • Fibroblast Growth Factor 4 / metabolism
  • Humans
  • Mice
  • Osteogenesis
  • Phosphorylation
  • Receptor, Fibroblast Growth Factor, Type 2 / chemistry
  • Receptor, Fibroblast Growth Factor, Type 2 / metabolism*
  • Receptor, Fibroblast Growth Factor, Type 3 / chemistry
  • Receptor, Fibroblast Growth Factor, Type 3 / metabolism
  • Recombinant Proteins / chemistry
  • Signal Transduction*

Substances

  • CCN2 protein, human
  • FGF4 protein, human
  • Fibroblast Growth Factor 4
  • Recombinant Proteins
  • Fibroblast Growth Factor 2
  • Connective Tissue Growth Factor
  • FGFR2 protein, human
  • FGFR3 protein, human
  • Receptor, Fibroblast Growth Factor, Type 2
  • Receptor, Fibroblast Growth Factor, Type 3
  • Extracellular Signal-Regulated MAP Kinases