Hobson J P, Rosenfeldt H M, Barak L S, Olivera A, Poulton S, Caron M G, Milstien S, Spiegel S
Department of Biochemistry and Molecular Biology, Georgetown University Medical Center, Washington, DC 20007, USA.
Science. 2001 Mar 2;291(5509):1800-3. doi: 10.1126/science.1057559.
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.
EDG-1是一种针对1-磷酸鞘氨醇（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，该因子刺激鞘氨醇激酶并增加细胞内SPP，这依赖于EDG-1的表达。edg-1的缺失或鞘氨醇激酶的抑制会抑制对PDGF的趋化作用，也会抑制小GTP酶Rac的激活，而Rac对于片状伪足的突出和向前运动至关重要。此外，通过β-抑制蛋白的转位和EDG-1的磷酸化测量发现，PDGF激活了EDG-1。我们的结果揭示了受体交叉通讯的作用，其中受体酪氨酸激酶对GPCR的激活对细胞运动至关重要。
