期刊
CELLULAR AND MOLECULAR LIFE SCIENCES
卷 63, 期 23, 页码 2871-2879出版社
SPRINGER BASEL AG
DOI: 10.1007/s00018-006-6379-x
关键词
Akt; GSK-3 beta; IEC-6; migration; polyamines
资金
- NIDDK NIH HHS [DK 52784] Funding Source: Medline
The rapid migration of intestinal epithelial cells (IEC) is important for the healing of mucosal wounds. We have previously shown that polyamine depletion inhibits migration of IEC-6 cells. Akt activation and its downstream target GSK-3 beta have been implicated in the regulation of migration. Here we investigated the significance of elevated phosphatidylinositol 3-kinase (PI3K)/Akt signaling on migration of polyamine-depleted cells. Polyamine-depleted cells had high Akt (Ser473) and GSK-3 beta (Ser9) phosphorylation. Pretreatment with 20 mu M LY294002 (PI3K inhibitor) for 30 min inhibited phosphorylation of Akt, increased migration by activating Rac1 in polyamine-depleted IEC-6 cells, and restored the actin structure similar to that in cells grown in control medium. Treatment of cells with a GSK-3 beta inhibitor (AR-A014418) altered the actin cytoskeleton and inhibited migration, mimicking the effects of polyamine depletion. Thus, our results indicate that sustained activation of Akt in response to polyamine depletion inhibits migration through GSK-3 beta and Rac1.
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