期刊
EMBO REPORTS
卷 7, 期 7, 页码 704-709出版社
WILEY
DOI: 10.1038/sj.embor.7400737
关键词
plexin; semaphorin; R-Ras GAP; PI(3)K; Akt; GSK-3 beta
Plexins are receptors for the axonal guidance molecules known as semaphorins, and the semaphorin 4D (Sema4D) receptor plexin-B1 induces repulsive responses by functioning as an R-Ras GTPase-activating protein (GAP). Here we characterized the downstream signalling of plexin-B1-mediated R-Ras GAP activity, inducing growth cone collapse. Sema4D suppressed R-Ras activity in hippocampal neurons, in parallel with dephosphorylation of Akt and activation of glycogen synthase kinase (GSK)-3 beta. Ectopic expression of the constitutively active mutant of Akt or treatment with GSK-3 inhibitors suppressed the Sema4D-induced growth cone collapse. Constitutive activation of phosphatidyl-inositol-3-OH kinase (PI(3)K), an upstream kinase of Akt and GSK-3 beta, also blocked the growth cone collapse. The R-Ras GAP activity was necessary for plexin-B1-induced dephosphorylation of Akt and activation of GSK-3 beta and was also required for phosphorylation of a downstream kinase of GSK-3 beta, collapsin response mediator protein-2. Plexin-A1 also induced dephosphorylation of Akt and GSK-3 beta through its R-Ras GAP activity. We conclude that plexin-B1 inactivates PI(3) K and dephosphorylates Akt and GSK-3 beta through R-Ras GAP activity, inducing growth cone collapse.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据