Receptor Specificity of the Fibroblast Growth Factor Family

TLDR

Fibroblast growth factors are essential for mammalian development, with nine ligands and four receptors expressed in distinct spatial and temporal patterns and regulated by ligand specificity, heparan sulfate proteoglycans, and receptor signaling capacity. The study aimed to identify relevant ligand–receptor pairs by engineering cell lines expressing major splice variants of all known FGF receptors. The engineered cell lines were used to assay mitogenic activity of the nine ligands, and relative activities were quantified using FGF 1 as an internal standard. FGF 1 uniquely activates all receptor splice variants, and the relative activities of other FGFs were measured, providing a biochemical basis for understanding FGF signaling in development, physiology, and disease.

Abstract

Fibroblast growth factors (FGFs) are essential molecules for mammalian development. The nine known FGF ligands and the four signaling FGF receptors (and their alternatively spliced variants) are expressed in specific spatial and temporal patterns. The activity of this signaling pathway is regulated by ligand binding specificity, heparan sulfate proteoglycans, 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 major 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 activate all FGF receptor splice variants. Using FGF 1 as 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 for determining developmental, physiological, and pathophysiological processes that involve FGF signaling pathways.