Role of the sphingosine-1-phosphate receptor EDG-1 in PDGF-induced cell motility
Role of the sphingosine-1-phosphate receptor EDG-1 in PDGF-induced cell motility
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DOI：
10.1126/science.1057559
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发表时间：
2001-03-02
期刊：
影响因子：
56.9
通讯作者：
Spiegel, S
中科院分区：
文献类型：
--
作者：
Hobson, JP;Rosenfeldt, HM;Spiegel, S
EDG-1是鞘氨醇-1-磷酸（SPP）的异源三聚体鸟嘌呤核苷酸结合蛋白偶联受体（GPCR）。细胞向血小板衍生生长因子（PDGF）迁移。其刺激鞘氨醇激酶并增加细胞内SPP，依赖于EDG-1的表达。edg-1的缺失或鞘氨醇激酶的抑制抑制对PDGF的趋化性和小的鸟苷三磷酸酶Rac的激活，这是必不可少的板状伪足的突起和向前运动。此外，PDGF激活EDG-1，如通过β-抑制蛋白的移位和EDG-1的磷酸化所测量的。我们的研究结果揭示了受体交叉通信的作用，其中受体酪氨酸激酶激活GPCR对细胞运动至关重要。
EDG-1 is a heterotrimeric guanine nucleotide binding protein-coupled receptor (GPCR) for sphingosine-1-phosphate (SPP). Cell migration toward platelet-derived growth factor (PDGF). which stimulates sphingosine kinase and increases intracellular SPP, was dependent on expression of EDG-1. Deletion of edg-1 or inhibition of sphingosine kinase suppressed chemotaxis toward PDGF and also activation of the small guanosine triphosphatase Rac, which is essential for protrusion of lamellipodia and forward movement. Moreover, PDGF activated EDG-1, as measured by translocation of beta -arrestin and phosphorylation of EDG-1. Our results reveal a role for receptor cross-communication in which activation of a GPCR by a receptor tyrosine kinase is critical for cell motility.