Kan M, Wang F, Xu J, Crabb J W, Hou J, McKeehan W L
W. Alton Jones Cell Science Center, Inc. Lake Placid, NY 12946.
Science. 1993 Mar 26;259(5103):1918-21. doi: 10.1126/science.8456318.
Heparin or heparin-like heparan sulfate proteoglycans are obligatory for activity of the heparin-binding fibroblast growth factor (FGF) family. Heparin interacts independently of FGF ligand with a specific sequence (K18K) in one of the immunoglobulin-like loops in the extracellular domain of the FGF receptor tyrosine kinase transmembrane glycoprotein. A synthetic peptide corresponding to K18K inhibited heparin and heparin-dependent FGF binding to the receptor. K18K and an antibody to K18K were antagonists of FGF-stimulated cell growth. Point mutations of lysine residues in the K18K sequence abrogated both heparin- and ligand-binding activities of the receptor kinase. The results indicate that the FGF receptor is a ternary complex of heparan sulfate proteoglycan, tyrosine kinase transmembrane glycoprotein, and ligand.
肝素或类肝素硫酸乙酰肝素蛋白聚糖对于肝素结合成纤维细胞生长因子（FGF）家族的活性是必不可少的。肝素独立于FGF配体，与FGF受体酪氨酸激酶跨膜糖蛋白细胞外结构域中一个免疫球蛋白样环的特定序列（K18K）相互作用。对应于K18K的合成肽抑制肝素和肝素依赖性FGF与受体的结合。K18K和抗K18K抗体是FGF刺激的细胞生长的拮抗剂。K18K序列中赖氨酸残基的点突变消除了受体激酶的肝素结合和配体结合活性。结果表明，FGF受体是硫酸乙酰肝素蛋白聚糖、酪氨酸激酶跨膜糖蛋白和配体的三元复合物。
