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.
Copyright © 2012 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Cell Line
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Chondrocytes / metabolism
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Connective Tissue Growth Factor / chemistry
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Connective Tissue Growth Factor / metabolism*
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Connective Tissue Growth Factor / pharmacology
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Extracellular Signal-Regulated MAP Kinases / metabolism
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Fibroblast Growth Factor 2 / chemistry
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Fibroblast Growth Factor 2 / metabolism
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Fibroblast Growth Factor 2 / pharmacology
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Fibroblast Growth Factor 4 / chemistry
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Fibroblast Growth Factor 4 / metabolism
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Humans
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Mice
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Osteogenesis
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Phosphorylation
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Receptor, Fibroblast Growth Factor, Type 2 / chemistry
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Receptor, Fibroblast Growth Factor, Type 2 / metabolism*
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Receptor, Fibroblast Growth Factor, Type 3 / chemistry
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Receptor, Fibroblast Growth Factor, Type 3 / metabolism
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Recombinant Proteins / chemistry
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Signal Transduction*
Substances
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CCN2 protein, human
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FGF4 protein, human
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Fibroblast Growth Factor 4
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Recombinant Proteins
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Fibroblast Growth Factor 2
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Connective Tissue Growth Factor
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FGFR2 protein, human
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FGFR3 protein, human
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Receptor, Fibroblast Growth Factor, Type 2
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Receptor, Fibroblast Growth Factor, Type 3
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Extracellular Signal-Regulated MAP Kinases