The role of syndecan cytoplasmic domain in basic fibroblast growth factor-dependent signal transduction
The role of syndecan cytoplasmic domain in basic fibroblast growth factor-dependent signal transduction
复制标题
DOI：
10.1074/jbc.274.34.24417
复制
发表时间：
1999-08-20
影响因子：
4.8
通讯作者：
Simons, M
中科院分区：
文献类型：
--
作者：
Volk, R;Schwartz, JJ;Simons, M
为了确定多配体蛋白聚糖-4胞质mic结构域在介导碱性成纤维细胞生长因子（bFGF）信号传导中所起的作用，使用永生化人细胞（ECV）来产生表达编码多配体蛋白聚糖-4（S4）、多配体蛋白聚糖-1（S1）、磷脂酰肌醇蛋白聚糖-1（G1）、或由连接到多配体蛋白聚糖-4（G1-S4 c）的跨膜/胞质结构域的磷脂酰肌醇蛋白聚糖-1的胞质结构域和连接到磷脂酰肌醇蛋白聚糖-1（G1-S4 c）的多配体蛋白聚糖-4的胞质结构域组成的嵌合蛋白。1糖基磷脂酰肌醇（GPI）锚序列（S4-GPI）。使用载体转导的细胞（VC）作为对照。所有这些蛋白聚糖的表达（除了载体对照）显著增加了细胞相关硫酸乙酰肝素质量和低亲和力bFGF结合位点的数量。然而，在低血清培养基中，加入bFGF刺激表达S4和G1-S4 c构建体的细胞的生长和迁移，但不刺激G1、S1、S4-GPI或VC细胞。使用基质胶生长测定获得了类似的结果。S4结构上硫酸乙酰肝素附着位点的突变消除了多配体蛋白聚糖-4依赖性bFGF反应的增强。我们的结论是syndecan-4的胞质尾区在bFGF介导的信号转导中起着重要的作用。
To determine the role played by syndecan-4 cytoplasmic mic domain in the mediation of basic fibroblast growth factor (bFGF) signaling, immortalized human cells (ECV) were used to generate cell lines expressing constructs encoding full-length sequences for syndecan-4 (S4), syndecan-1 (S1), glypican-1 (G1), or chimeric proteins consisting of the ectoplasmic domain of glypican-1 linked to the transmembrane/cytoplasmic domain of syndecan-4 (G1-S4c) and the ectoplasmic domain of syndecan-4 linked to the glypican-1 glycosylphosphatidylinositol (GPI) anchor sequence (S4-GPI). Vector-transduced cells (VC) were used as controls. Expression of all these proteoglycans (except for the vector control) significantly increased cell-associated heparan sulfate mass and the number of low affinity bFGF-binding sites. However, in low serum medium, the addition of bFGF stimulated growth and migration of cells expressing S4 and G1-S4c constructs but not G1, S1, S4-GPI, or VC cells. Similar results were obtained using Matrigel growth assays. Mutations of heparan sulfate attachment sites on S4 construct abolished syndecan-4-dependent augmentation of bFGF responses. We conclude that cytoplasmic tail of syndecan-4 plays an important role in bFGF-mediated signal transduction.