Ephrin-B reverse signaling is mediated by a novel PDZ-RGS protein and selectively inhibits G protein-coupled chemoattraction
Ephrin-B reverse signaling is mediated by a novel PDZ-RGS protein and selectively inhibits G protein-coupled chemoattraction
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DOI：
10.1016/s0092-8674(01)00297-5
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发表时间：
2001-04-06
期刊：
影响因子：
64.5
通讯作者：
Flanagan, JG
中科院分区：
文献类型：
--
作者：
Lu, Q;Sun, EE;Flanagan, JG
跨膜B肾上腺素和它们的Eph受体是双向信号。然而，无论是细胞生物学效应还是反向信号的信号转导机制都不是很清楚。我们描述了一种细胞质蛋白PDZ-RGS3，它通过PDZ结构域与B肾上腺素结合，并具有异源三聚体G蛋白信号转导(RGS)结构域的调节因子。PDZ-RGS3可介导EPhin-B胞浆尾部的信号传导。SDF-1是一种带有G蛋白偶联受体的趋化因子，对小脑颗粒细胞具有趋化作用，其作用可被可溶性EphB受体选择性抑制。这项研究揭示了一条将反向信号与细胞指导联系起来的途径，揭示了G蛋白的一种新的控制模式，并展示了一种选择性调节对神经元指导线索的反应性的机制。
Transmembrane B ephrins and their Eph receptors signal bidirectionally. However, neither the cell biological effects nor signal transduction mechanisms of the reverse signal are well understood. We describe a cytoplasmic protein, PDZ-RGS3, which binds B ephrins through a PDZ domain, and has a regulator of heterotrimeric G protein signaling (RGS) domain. PDZ-RGS3 can mediate signaling from the ephrin-B cytoplasmic tail. SDF-1, a chemokine with a G protein-coupled receptor, or BDNF, act as chemoattractants for cerebellar granule cells, with SDF-1 action being selectively inhibited by soluble EphB receptor. This study reveals a pathway that links reverse signaling to cellular guidance, uncovers a novel mode of control for G proteins, and demonstrates a mechanism for selective regulation of responsiveness to neuronal guidance cues.