Akt/PKB Regulates Actin Organization and Cell Motility via Girdin/APE

详细信息    查看全文

• 作者：Atsushi Enomoto ; Hideki Murakami ; Naoya Asai ; Nobuhiro Morone ; Takashi Watanabe ; Kumi Kawai ; Yoshiki Murakumo ; Jiro Usukura ; Kozo Kaibuchi ; Masahide Takahashi
• 关键词：CELLBIO ; CELLCYCLE
• 刊名：Developmental Cell
• 出版年：2005
• 出版时间：September 2005
• 年：2005
• 卷：9
• 期：3
• 页码：389-402
• 全文大小：1015 K

文摘

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.