Copper and calcium binding motifs in the extracellular domains of fibroblast growth factor receptors.
High affinity fibroblast growth factor (FGF) receptors contain a cluster of acidic amino acids in their extracellular domains that is reminiscent of the calcium binding domains of some cell adhesion molecules. Based on this observation, we used a calcium blotting technique to show that FGFR-1 binds calcium and that calcium binding is not observed in a mutagenized form of the receptor that lacks the acidic box region. The acidic box also binds other divalent cations, including copper. This latter interaction appears unique since the binding of copper to FGFR-1 mediates the binding of the receptor to immobilized heparin. While this observation may help explain the angiogenic properties of copper, divalent cation binding to FGF receptors may also mediate the interaction between FGF receptors, cell adhesion molecules and other proteoglycan components of the extracellular matrix.
Patstone
G
G
Department of Cell Biology, The Scripps Research Institute, La Jolla, California 92037, USA.
Maher
P
P
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002118:Calcium / Q000378:metabolism*; D002846:Chromatography, Affinity; D003300:Copper / Q000378:metabolism*; D017931:DNA Primers; D005346:Fibroblast Growth Factors / Q000378:metabolism; D007700:Kinetics; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D016133:Polymerase Chain Reaction; D020794:Receptor Protein-Tyrosine Kinases; D051496:Receptor, Fibroblast Growth Factor, Type 1; D017468:Receptors, Fibroblast Growth Factor / Q000096:biosynthesis / Q000737:chemistry* / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism; D012685:Sepharose / Q000031:analogs & derivatives; D018411:Spodoptera; D014162:Transfection
D017931:DNA Primers; D017468:Receptors, Fibroblast Growth Factor; D011993:Recombinant Fusion Proteins; C037405:heparin-sepharose; D005346:Fibroblast Growth Factors; D003300:Copper; D012685:Sepharose; D020794:Receptor Protein-Tyrosine Kinases; D051496:Receptor, Fibroblast Growth Factor, Type 1; D002118:Calcium