PI3K induced actin filament remodeling through Akt and p70S6K1: implication of essential role in cell migration.
This study was designed to identify the molecular mechanisms of phosphatidylinositol 3-kinase (PI3K)-induced actin filament remodeling and cell migration. Expression of active forms of PI3K, v-P3k or Myr-P3k, was sufficient to induce actin filament remodeling to lead to an increase in cell migration, as well as the activation of Akt in chicken embryo fibroblast (CEF) cells. Either the inhibition of PI3K activity using a PI3K-specific inhibitor, LY-294002, or the disruption of Akt activity restored the integrity of actin filaments in CEF cells and inhibited PI3K-induced cell migration. We also found that expression of an activated form of Akt (Myr-Akt) was sufficient to remodel actin filaments to lead to an increase in cell migration, which was unable to be inhibited by the presence of LY-294002. Furthermore, we found that p70S6K1 kinase was a downstream molecule that can mediate the effects of both PI3K and Akt on actin filaments and cell migration. Overexpression of an active form of p70S6K1 was sufficient to induce actin filament remodeling and cell migration in CEF cells, which requires Rac activity. These results demonstrate that activation of PI3K activity alone is sufficient to remodel actin filaments to increase cell migration through the activation of Akt and p70S6K1 in CEF cells.
Qian
Yong
Y
Pathology and Physiology Research Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health/NIH, Morgantown, WV 26506, USA. yqian@cdc.gov
Corum
Linda
L
Meng
Qiao
Q
Blenis
John
J
Zheng
Jenny Z
JZ
Shi
Xianglin
X
Flynn
Daniel C
DC
Jiang
Bing-Hua
BH
D008841:Actin Cytoskeleton / Q000502:physiology*; D000818:Animals; D002465:Cell Movement / Q000502:physiology; D002642:Chick Embryo; D004789:Enzyme Activation / Q000502:physiology; D019869:Phosphatidylinositol 3-Kinases / Q000494:pharmacology / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000378:metabolism / Q000502:physiology*; D051057:Proto-Oncogene Proteins c-akt; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000502:physiology*; D020744:rac GTP-Binding Proteins / Q000502:physiology
D019869:Phosphatidylinositol 3-Kinases; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D020744:rac GTP-Binding Proteins