TY - JOUR
T1 - Akt/PKB regulates actin organization and cell motility via girdin/APE
AU - Enomoto, Atsushi
AU - Murakami, Hideki
AU - Asai, Naoya
AU - Morone, Nobuhiro
AU - Watanabe, Takashi
AU - Kawai, Kumi
AU - Murakumo, Yoshiki
AU - Usukura, Jiro
AU - Kaibuchi, Kozo
AU - Takahashi, Masahide
N1 - Funding Information:
We thank Y. Gotoh (University of Tokyo) for providing Akt cDNAs and helpful discussion, T. Fukuda (Tohoku University) for helpful discussion, M. Nakayama (Nagoya University) for discussions on migration assays, K. Kadomatsu and K. Ichihara (Nagoya University) for providing HT-1080 cells, and N. Saka and A. Muraki (Nagoya University) for help in characterization of Girdin. This work was supported by Grants-in-Aid for Center of Excellence (COE) Research, Scientific Research (A), and Scientific Research on Priority Area “Cancer” from the Ministry of Education, Culture, Sports, Science and Technology of Japan (to M.T.). A.E. is a fellow of the Japan Society for the Promotion of Science.
PY - 2005/9
Y1 - 2005/9
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/24144496081
UR - https://www.scopus.com/pages/publications/24144496081#tab=citedBy
U2 - 10.1016/j.devcel.2005.08.001
DO - 10.1016/j.devcel.2005.08.001
M3 - Article
C2 - 16139227
AN - SCOPUS:24144496081
SN - 1534-5807
VL - 9
SP - 389
EP - 402
JO - Developmental Cell
JF - Developmental Cell
IS - 3
ER -