RECEPTOR SPECIFICITY OF THE FIBROBLAST GROWTH-FACTOR FAMILY

Fibroblast growth factors (FGFs) are essential molecules for mammalian development. The nine known FGF ligands and the four signaling FGF re ceptors (and their alternatively spliced variants) are expressed in sp ecific spatial and temporal patterns, The activity of this signaling p athway is regulated by ligand binding specificity, heparan sulfate pro teoglycans, and the differential signaling capacity of individual FGF receptors. To determine potentially relevant ligand-receptor pairs we have engineered mitogenically responsive cell lines expressing the maj or splice variants of all the known FGF receptors. We have assayed the mitogenic activity of the nine known FGF ligands on these cell lines. These studies demonstrate that FGF 1 is the only FGF that can activat e all FGF receptor splice variants. Using FGF las an internal standard we have determined the relative activity of all the other members of the FGF family. These data should serve as a biochemical foundation fo r determining developmental, physiological, and patho physiological pr ocesses that involve FGF signaling pathways.