LIGAND-BINDING BY FIBROBLAST GROWTH-FACTOR RECEPTORS INVESTIGATED USING CHIMERIC RECEPTOR MOLECULES

In order to map in detail the ligand binding sites of fibroblast growt h factor receptor 2 (FGFR2) and keratinocyte growth factor receptor (K GFR), we have generated receptor molecules that are chimeric within th e membrane proximal sequence that varies between them. The chimeric mo lecules are found to bind aFGF with a greater than 5-fold difference i n affinity, indicating that there is coupling between the chimeric reg ions with respect to aFGF binding. Further, binding of bFGF and KGF is abolished in the chimeras, showing that the binding site for these li gands requires the whole of the 48- or 50- amino acid variable sequenc e to be intact. Direct interactions between the different regions exch anged in the chimeras are most probably involved in forming KGF or bFG F binding sites.