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The fibroblast growth factor (FGF) family consists of at least seven closely related polypeptide mitogens which exert their activities by binding and activation of specific cell surface receptors. Unanswered questions have been whether there are multiple FGF receptors and what factors determine binding specificity and biological response. We report the(More)
Heparin is required for fibroblast growth factor (FGF) stimulation of biological responses. Using isothermal titration calorimetry, we show that acidic FGF (aFGF) forms a 1:1 complex with the soluble extracellular domain of FGF receptor (FGFR). Heparin exerts its effect by binding to many molecules of aFGF. The resulting aFGF-heparin complex can bind to(More)
We have previously isolated a human gene from an endothelial cell cDNA library encoding a putative tyrosine kinase; we have designated this gene the fms-like gene (FLG). To analyze the gene product(s) of FLG, we have generated rabbit polyclonal antibodies directed against a synthetic peptide from FLG and used it to immunoprecipitate biosynthetically labeled(More)
Tumor DNA samples from 387 breast carcinomas have been investigated for amplification of BEK and FLG genes, both of which have been shown to code for cell surface receptors to FGFs. BEK and FLG were found amplified in 11.5 and 12.7% of breast tumors respectively. Statistical analysis, performed on the subset of 297 primary cancers without presurgical(More)
Recent evidence shows that different fibroblast growth factors (FGF) bind with similar high affinities to two FGF receptors (FGFR) called flg and bek. In order to explore the mechanism of FGFR tyrosine autophosphorylation, we have generated cell lines which co-express a kinase-negative mutant of FGFR and an active form of FGFR. The following transfected NIH(More)
We present here the complete primary structure of human gp330, the human variant of the principal kidney autoantigen causing Heymann membranous glomerulonephritis in rats. The deduced 4655 amino acid residues give a calculated molecular mass of 519636 Da for the mature protein and consists of a probable 25-amino-acid N-terminal signal peptide sequence, an(More)
We recently reported the cloning and overexpression of full-length forms of human fibroblast growth factor (FGF) receptors, bek and flg. These receptors contain three immunoglobulin (Ig)-like domains and an unusual acidic motif in the extracellular region, a single transmembrane segment and a protein tyrosine kinase cytoplasmic domain containing a 14 amino(More)
Voltage-gated sodium channels (NaChs) are relevant targets for pain, epilepsy, and a variety of neurological and cardiac disorders. Traditionally, it has been difficult to develop structure-activity relationships for NaCh inhibitors due to rapid channel kinetics and state-dependent compound interactions. Membrane potential (Vm) dyes in conjunction with a(More)
Heparin potentiates the mitogenic activity of acidic fibroblast growth factor (aFGF) by 20-100 fold but mechanisms detailing this potentiation have not yet been fully elucidated. We report that heparin increases the binding affinity of aFGF for the two cloned and overexpressed human FGF receptors, flg and bek, by 2-3 fold. This increase in binding affinity,(More)