An inactive pool of GSK-3 at the leading edge of growth cones is implicated in Semaphorin 3A signaling.
An inactive pool of GSK-3 at the leading edge of growth cones is implicated in Semaphorin 3A signaling.
复制标题
DOI：
10.1083/jcb.200201098
复制
发表时间：
2002-04-15
影响因子：
7.8
通讯作者：
Doherty, Patrick
中科院分区：
文献类型：
--
作者：
Eickholt, Britta J;Walsh, Frank S;Doherty, Patrick
糖原合成酶激酶（GSK）-3是一种丝氨酸/苏氨酸激酶，它在胚胎发育的多个方面以及一些生长因子信号级联中都有涉及。我们现在报道，该酶的一种无活性的磷酸化库在神经元和非神经元细胞中都与F - 肌动蛋白共定位。轴突导向因子3A（Sema 3A）是一种抑制轴突生长的分子，它在神经元生长锥的前沿以及对Sema 3A有反应的人乳腺癌细胞中激活GSK - 3，这表明GSK - 3的活性可能在将Sema 3A信号与细胞运动性的变化相耦合中起作用。我们表明三种不同的GSK - 3拮抗剂（氯化锂、SB - 216763和SB - 415286）能够抑制由Sema 3A诱导的生长锥塌陷反应。这些研究揭示了细胞中无活性GSK - 3的一种新的区室化，并首次证明了在Sema 3A信号转导途径中GSK - 3活性的必要性。
Glycogen synthase kinase (GSK)-3 is a serine/threonine kinase that has been implicated in several aspects in embryonic development and several growth factor signaling cascades. We now report that an inactive phosphorylated pool of the enzyme colocalizes with F-actin in both neuronal and nonneuronal cells. Semaphorin 3A (Sema 3A), a molecule that inhibits axonal growth, activates GSK-3 at the leading edge of neuronal growth cones and in Sema 3A–responsive human breast cancer cells, suggesting that GSK-3 activity might play a role in coupling Sema 3A signaling to changes in cell motility. We show that three different GSK-3 antagonists (LiCl, SB-216763, and SB-415286) can inhibit the growth cone collapse response induced by Sema 3A. These studies reveal a novel compartmentalization of inactive GSK-3 in cells and demonstrate for the first time a requirement for GSK-3 activity in the Sema 3A signal transduction pathway.