Allen Benjamin L, Rapraeger Alan C
Department of Pathology and Laboratory Medicine, University of Wisconsin, Madison, WI 53706, USA.
J Cell Biol. 2003 Nov 10;163(3):637-48. doi: 10.1083/jcb.200307053.
Heparan sulfate (HS) interacts with diverse growth factors, including Wnt, Hh, BMP, VEGF, EGF, and FGF family members, and is a necessary component for their signaling. These proteins regulate multiple cellular processes that are critical during development. However, a major question is whether developmental changes occur in HS that regulate the activity of these factors. Using a ligand and carbohydrate engagement assay, and focusing on FGF1 and FGF8b interactions with FGF receptor (FR)2c and FR3c, this paper reveals global changes in HS expression in mouse embryos during development that regulate FGF and FR complex assembly. Furthermore, distinct HS requirements are identified for both complex formation and signaling for each FGF and FR pair. Overall, these results suggest that changes in HS act as critical temporal regulators of growth factor and morphogen signaling during embryogenesis.
硫酸乙酰肝素（HS）与多种生长因子相互作用，包括Wnt、Hh、BMP、VEGF、EGF和FGF家族成员，并且是其信号传导所必需的成分。这些蛋白质调节发育过程中至关重要的多个细胞过程。然而，一个主要问题是，在调节这些因子活性的HS中是否会发生发育变化。本文使用配体和碳水化合物结合试验，并聚焦于FGF1和FGF8b与FGF受体（FR）2c和FR3c的相互作用，揭示了小鼠胚胎发育过程中HS表达的整体变化，这些变化调节FGF和FR复合物的组装。此外，还确定了每对FGF和FR在复合物形成和信号传导方面对HS有不同的要求。总体而言，这些结果表明，HS的变化在胚胎发生过程中作为生长因子和形态发生素信号传导的关键时间调节剂。
