Structural and functional specificity of FGF receptors

Abstract

Fibroblast growth factors (FGFs) represent a group of polypeptide mitogens eliciting a wide variety of responses depending on the target cell type. The knowledge of the cell surface receptors mediating the effects of FGFs has recently expanded remarkably. Perhaps not surprisingly, the complexity of the FGF family and FGF induced responses is reflected in the diversity and redundancy of the FGF receptors. The molecular cloning of the signal transducing receptors for fibroblast growth factors has revealed a tyrosine kinase gene family with at least four members. Differential splicing and polyadenylation creates further diversity in the FGF receptor system. These numerous receptor forms have both distinct and redundant properties. We are only now beginning to understand how the different receptors are activated by the various FGFs and how they are expressed by various cells and tissues. FGF binding to the tyrosine kinase receptors needs the assistance of heparan sulphate side chains of proteoglycans present at the cell surface and in the extracellular matrix. As several other growth factors share the heparin binding property of FGFs, the dual receptor system for FGFs might be an example of a more widely used principle.