Syndecan-4 Regulates Subcellular Localization of mTOR Complex2 and Akt Activation in a PKCα-Dependent Manner in Endothelial Cells

被引：99

作者：

Partovian, Chohreh ^{[1
,2
]}

Ju, Rong ^{[1
,2
]}

Zhuang, Zhen W. ^{[1
,5
]}

Martin, Kathleen A. ^{[4
,6
]}

Simons, Michael ^{[1
,2
,3
,4
]}

机构：

[1] Dartmouth Hitchcock Med Ctr, Dartmouth Med Sch, Angiogenesis Res Ctr, Lebanon, NH 03756 USA

[2] Dartmouth Hitchcock Med Ctr, Dartmouth Med Sch, Cardiol Sect, Lebanon, NH 03756 USA

[3] Dartmouth Hitchcock Med Ctr, Dartmouth Med Sch, Dept Med, Lebanon, NH 03756 USA

[4] Dartmouth Hitchcock Med Ctr, Dartmouth Med Sch, Dept Pharmacol & Toxicol, Lebanon, NH 03756 USA

[5] Dartmouth Hitchcock Med Ctr, Dartmouth Med Sch, Dept Radiol, Lebanon, NH 03756 USA

[6] Dartmouth Hitchcock Med Ctr, Dartmouth Med Sch, Dept Surg, Lebanon, NH 03756 USA

来源：

MOLECULAR CELL | 2008年 / 32卷 / 01期

关键词：

D O I：

10.1016/j.molcel.2008.09.010

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Mammalian target of rapamycin (mTOR) activity is regulated by assembly of two functionally distinct complexes, mTORC1 and mTORC2. In syndecan-4 (S4) null endothelial cells, mTORC2 activity is reduced, resulting in decreased Akt activation, while mTORC1 activity is increased. Levels of rictor, mLST8, and mSin-1 are unchanged in total cell lysates but decreased in the rafts of S4(-/-) endothelial cells, as is the level of PKC alpha. Expression of myristoylated-PKC alpha in S4(-/-) cells restores rictor, mLST8, and mSin-1 presence in the rafts and rescues Akt phosphorylation. PKC alpha knockdown mimics the effect of S4 deletion on mTORC2 localization and Akt activation. Reduced mTORC2 activity in S4(-/-) endothelial cells results in decreased FoxO1/3a and eNOS phosphorylation, decreased endothelial cell size, and increased arterial blood pressure in S4(-/-) mice. Thus, S4-dependent targeting of PKC alpha to the plasma membrane is required for recruitment of mTORC2 components to the rafts and Akt activation.

引用

页码：140 / 149

页数：10

共 32 条

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