Akt/PKB regulates actin organization and cell motility via Girdin/APE.
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.
Enomoto
Atsushi
A
Department of Pathology, Center for Neurological Disease and Cancer, Nagoya University Graduate School of Medicine, Showa-ku, Aichi, Japan.
Murakami
Hideki
H
Asai
Naoya
N
Morone
Nobuhiro
N
Watanabe
Takashi
T
Kawai
Kumi
K
Murakumo
Yoshiki
Y
Usukura
Jiro
J
Kaibuchi
Kozo
K
Takahashi
Masahide
M
D000199:Actins / Q000378:metabolism*; D000818:Animals; D019556:COS Cells; D002462:Cell Membrane / Q000378:metabolism; D002465:Cell Movement / Q000502:physiology*; D002522:Chlorocebus aethiops; D006801:Humans; D008840:Microfilament Proteins; D008854:Microscopy, Electron; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D014709:Vero Cells; D033921:Vesicular Transport Proteins / Q000235:genetics / Q000378:metabolism*
D000199:Actins; C502451:CCDC88A protein, human; D008840:Microfilament Proteins; D011518:Proto-Oncogene Proteins; D034741:RNA, Small Interfering; D033921:Vesicular Transport Proteins; C494918:AKT1 protein, human; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt