Receptor Tyrosine Kinase Architecture
The fibroblast growth factor family, composed of 18 members at present, is involved in a myriad of physiological and pathological processes from development to adulthood. The downstream signaling effects of fibroblast growth factor are mediated by four fibroblast growth factor receptors (FGFR1, FGFR2, FGFR3, and FGFR4), which consist of (i) an extracellular ligand binding portion composed of three immunoglobulin like domains (D1-D3), (ii) a single transmembrane helix, and (iii) a cytoplasmic portion with tyrosine kinase activity. Like other receptor tyrosine kinases, FGFR dimerization is a critical step in receptor activation and downstream signaling. In addition to ligand binding, this process requires heparan sulfate proteoglycans or heparin. Models for FGFR dimerization have recently been proposed based on crystal structures of FGF-FGFR-heparin. Schematic diagram of fibroblast growth factor receptors. D1, D2, and D3 represent immunoglobulin-like domains 1, 2, and 3. SP represents the signal peptide; TM represents the transmembrane helix; JM represents the juxtamembrane region. The heparin-binding site in D2 is marked by a thick black line.