COPPER AND CALCIUM-BINDING MOTIFS IN THE EXTRACELLULAR DOMAINS OF FIBROBLAST GROWTH-FACTOR RECEPTORS

High affinity fibroblast growth factor (FGF) receptors contain a clust er of acidic amino acids in their extracellular domains that is remini scent of the calcium binding domains of some cell adhesion molecules. Based on this observation, we used a calcium blotting technique to sho w that FGFR-1 binds calcium and that calcium binding is not observed i n a mutagenized form of the receptor that lacks the acidic box region. The acidic box also binds other divalent cations, including copper. T his latter interaction appears unique since the binding of copper to F GFR-1 mediates the binding of the receptor to immobilized heparin. Whi le this observation may help explain the angiogenic properties of copp er, divalent cation binding to FGF receptors may also mediate the inte raction between FGF receptors, cell adhesion molecules and other prote oglycan components of the extracellular matrix.