Linker region of Akt1/protein kinase Bα mediates platelet-derived growth factor-induced translocation and cell migration

被引：27
作者：
Kim, Eun Kyoung [1 ]
Tucker, David F. [2 ]
Yun, Sung Ji [1 ]
Do, Kee Hun [1 ]
Kim, Min Sung [1 ]
Kim, Jae Ho [1 ]
Kim, Chi Dae [1 ]
Birnbaum, Morris J. [2 ]
Bae, Sun Sik [1 ]
机构：
[1] Pusan Natl Univ, Sch Med, Dept Pharmacol, Med Res Inst,MRC Ischem Tissue Regenerat, Pusan 602739, South Korea
[2] Univ Penn, Sch Med, Howard Hughes Med Inst, Philadelphia, PA 19104 USA
来源：
CELLULAR SIGNALLING | 2008年 / 20卷 / 11期
关键词：
Migration; PI3K; Akt/PKB; Linker region; PDGF;
D O I：
10.1016/j.cellsig.2008.07.012
中图分类号：
Q2 [细胞生物学];
学科分类号：
071009 ; 090102 ;
摘要：
The phosphatidylinositol 3-kinase (PI3K) signaling pathway(s) is activated by a variety of agonists to regulate cell migration. Here, we show that the stimulation of mouse embryonic fibroblasts with plate let-derived growth factor (PDGF) induces migration in a PI3K-dependent manner. Cells lacking Akt1/PKB alpha exhibit impaired migration and peripheral ruffling in response to PDGF stimulation, whereas cells lacking Akt2/PKB beta are normal. In addition, over-expression of Akt1/PKB alpha but not Akt2/PKB beta is sufficient to restore PDGF-induced cell migration in an Akt1/PKB alpha and Akt2/PKB beta deficient background. In response to PDGF stimulation, Akt1/PKB alpha selectively translocates to membrane ruffles, however, this localization is abrogated by substituting the linker region of Akt1/PKB alpha. Similarly, expression of an Akt2/PKB alpha chimera containing the linker region of Akt1/PKB alpha restored PDGF-induced migration in cells lacking both Akt1/PKB alpha and Akt2/PKB beta. Finally, over-expression of constitutively active Rac rescues PDGF-induced migration defects in cells lacking Akt1/PKB alpha. Given these results, we Suggest that Akti/PKB alpha controls cell migration by selectively translocating to the leading edge and activating Rac. (c) 2008 Elsevier Inc. All rights reserved.
引用
收藏
页码：2030 / 2037
页数：8
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