Ligand-binding sites in Ig-like domains of receptor tyrosine kinases

Receptor tyrosine kinases are cell-bound, membrane-spanning receptors that transduce growth factor dependent signals to the intracellular environment. Their catalytic cytoplasmic domains share a high level of sequence similar ity, but their extracellular portions usually have a highly variable, multi ple-domain structure. In a growing number of cases immunoglobulin-like doma ins contained within the extracellular portion have been shown to contain t he ligand-binding site. In recent years experimental three-dimensional stru ctures have been determined for some of these domains, free or in complex w ith their ligand. Here we review current structural information on these im munoglobulin-like domains and the growth factors that bind to them, with an emphasis on the vascular endothelial growth factor, nerve growth factor, a nd fibroblast growth factor systems.