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 similarity, but their extracellular portions usually have a highly variable, multiple-domain structure. In a growing number of cases immunoglobulin-like domains contained within the extracellular portion have been shown to contain the ligand-binding site. In recent years experimental three-dimensional structures have been determined for some of these domains, free or in complex with their ligand. Here we review current structural information on these immunoglobulin-like domains and the growth factors that bind to them, with an emphasis on the vascular endothelial growth factor, nerve growth factor, and fibroblast growth factor systems.
Wiesmann
C
C
Genentech, Inc., Department of Protein Engineering, South San Francisco, CA 94080, USA.
Muller
Y A
YA
de Vos
A M
AM
D000595:Amino Acid Sequence; D001665:Binding Sites; D016228:Endothelial Growth Factors / Q000737:chemistry / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000737:chemistry / Q000378:metabolism; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D006801:Humans; D007074:Immunoglobulin G / Q000737:chemistry*; D008024:Ligands; D008222:Lymphokines / Q000737:chemistry / Q000378:metabolism; D008969:Molecular Sequence Data; D020794:Receptor Protein-Tyrosine Kinases / Q000737:chemistry* / Q000378:metabolism*; D051496:Receptor, Fibroblast Growth Factor, Type 1; D017468:Receptors, Fibroblast Growth Factor / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D013329:Structure-Activity Relationship; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D016326:Extracellular Matrix Proteins; D007074:Immunoglobulin G; D008024:Ligands; D008222:Lymphokines; D017468:Receptors, Fibroblast Growth Factor; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D016222:Fibroblast Growth Factor 2; C496348:FGFR1 protein, human; D020794:Receptor Protein-Tyrosine Kinases; D051496:Receptor, Fibroblast Growth Factor, Type 1