Akt/PKB regulates actin organization and cell motility via girdin/APE
Akt/PKB regulates actin organization and cell motility via girdin/APE
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DOI：
10.1016/j.devcel.2005.08.001
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发表时间：
2005-09-01
影响因子：
11.8
通讯作者：
Takahashi, M
中科院分区：
文献类型：
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作者：
Enomoto, A;Murakami, H;Takahashi, M
众所周知，丝氨酸/苏氨酸激酶Akt（也称为蛋白激酶B）是细胞存活和生长的重要调节剂，并且也已显示是不同生物体中细胞迁移所需的。然而，Akt促进细胞迁移的机制尚不清楚。在这里，我们确定了Akt底物，命名为Girdin/APE（Akt磷酸化增强子），这是一种肌动蛋白结合蛋白。Girdin广泛表达并在应力纤维和板状伪足的形成中起关键作用。Akt使Girdin中1416位的丝氨酸磷酸化，磷酸化的Girdin在迁移细胞的前缘积累。细胞表达突变Girdin，其中丝氨酸1416被替换为丙氨酸，形成异常细长的形状，并表现出有限的迁移和片状伪足形成。这些发现表明，Girdin是必不可少的肌动蛋白细胞骨架和细胞迁移的完整性，并提供了Akt和细胞运动之间的直接联系。
The serine/threonine kinase Akt (also called protein kinase B) is well known as an important regulator of cell survival and growth and has also been shown to be required for cell migration in different organisms. However, the mechanism by which Akt functions to promote cell migration is not understood. Here, we identify an Akt substrate, designated Girdin/APE (Akt-phosphorylation enhancer), which is an actin binding protein. Girdin expresses ubiquitously and plays a crucial role in the formation of stress fibers and lamellipodia. Akt phosphorylates serine at position 1416 in Girdin, and phosphorylated Girdin accumulates at the leading edge of migrating cells. Cells expressing mutant Girdin, in which serine 1416 was replaced with alanine, formed abnormal elongated shapes and exhibited limited migration and lamellipodia formation. These findings suggest that Girdin is essential for the integrity of the actin cytoskeleton and cell migration and provide a direct link between Akt and cell motility.