Köhl R, Antoine M, Olwin B B, Dickson C, Kiefer P
Ruhr-Universität Bochum, Medizinische Fakultät, Abteilung für Virologie, Universitätsstrasse 150, Gebäuole MA 6/130, D-44780 Bochum, Germany.
J Biol Chem. 2000 May 26;275(21):15741-8. doi: 10.1074/jbc.M903271199.
Expression of the cysteine-rich fibroblast growth factor (FGF) receptor (CFR) in COS-1 cells strongly inhibits the secretion of co-expressed FGF3. By using a column retention assay and affinity chromatography, we demonstrate that at physiological salt concentrations FGF3 binds with strong affinity to CFR in vivo and in vitro. Furthermore, to show that FGF3 binds to CFR in vivo, truncation mutants of CFR with changed subcellular distributions were shown to cause a similar redistribution of FGF3. Although CFR is a 150-kDa integral membrane glycoprotein that is primarily located in the Golgi apparatus, we show here that in COS-1 cells a substantial proportion of CFR is secreted. This is due to a carboxyl-terminal proteolytic cleavage that releases the intraluminal portion of the protein for secretion. However, the apparent size of the integral membrane and secreted CFR appears similar, since the loss of protein mass is balanced by a gain of complex carbohydrates. The released CFR is associated with the extracellular matrix through its affinity for glycosaminoglycans. These findings show that CFR can modulate the secretion of FGF3 and may control its biological activity by regulating its secretion.
富含半胱氨酸的成纤维细胞生长因子（FGF）受体（CFR）在COS-1细胞中的表达强烈抑制共表达的FGF3的分泌。通过柱保留分析和亲和层析，我们证明在生理盐浓度下，FGF3在体内和体外均与CFR具有强亲和力结合。此外，为了证明FGF3在体内与CFR结合，具有改变的亚细胞分布的CFR截短突变体被证明会导致FGF3发生类似的重新分布。尽管CFR是一种150 kDa的整合膜糖蛋白，主要位于高尔基体中，但我们在此表明，在COS-1细胞中，相当一部分CFR是分泌型的。这是由于羧基末端的蛋白水解切割释放了蛋白质的腔内部分以供分泌。然而，整合膜CFR和分泌型CFR的表观大小似乎相似，因为蛋白质质量的损失被复合碳水化合物的增加所平衡。释放的CFR通过其对糖胺聚糖的亲和力与细胞外基质相关联。这些发现表明，CFR可以调节FGF3的分泌，并可能通过调节其分泌来控制其生物学活性。
