Wegehingel Sabine, Zehe Christoph, Nickel Walter
Heidelberg University, Biochemistry Center, Germany.
FEBS Lett. 2008 Jul 9;582(16):2387-92. doi: 10.1016/j.febslet.2008.05.042. Epub 2008 Jun 5.
FGF-2 is a proangiogenic growth factor secreted by unconventional means. It is unknown why FGF-2 takes an ER/Golgi-independent secretory route. We find that secretion of FGF-2 via the ER/Golgi system causes post-translational modifications that prevent binding to heparan sulfate proteoglycans (HSPGs), an interaction that is critically important for both FGF-2 storage and signal transduction. This loss of function is due to artificial O-glycosylation mainly resulting in the addition of glycosaminoglycan chains of the chrondroitin sulfate type. Our findings suggest that the unconventional mechanism of FGF-2 export is an ancient pathway of protein secretion that, in the course of evolution, has been kept due to the inability of the classical secretory pathway to export FGF-2 in a functional form.
成纤维细胞生长因子-2（FGF-2）是一种通过非常规方式分泌的促血管生成生长因子。目前尚不清楚为何FGF-2采用不依赖内质网/高尔基体的分泌途径。我们发现，FGF-2通过内质网/高尔基体系统分泌会导致翻译后修饰，从而阻止其与硫酸乙酰肝素蛋白聚糖（HSPGs）结合，而这种相互作用对于FGF-2的储存和信号转导都至关重要。这种功能丧失是由于人为的O-糖基化，主要导致硫酸软骨素类型的糖胺聚糖链的添加。我们的研究结果表明，FGF-2的非常规分泌机制是一种古老的蛋白质分泌途径，在进化过程中，由于经典分泌途径无法以功能形式分泌FGF-2，该途径得以保留。
