Syndecan-4 Regulates Subcellular Localization of mTOR Complex2 and Akt Activation in a PKCα-Dependent Manner in Endothelial Cells
| Autor: | Rong Ju, Michael Simons, Kathleen A. Martin, Chohreh Partovian, Zhen W. Zhuang |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
Protein Kinase C-alpha
Biological Transport Active FOXO1 mTORC1 Biology Models Biological mTORC2 Article Cell Line Syndecan 1 Mice Membrane Microdomains Animals Growth Substances Molecular Biology Protein kinase B Cells Cultured PI3K/AKT/mTOR pathway Mice Knockout TOR Serine-Threonine Kinases Endothelial Cells Cell Biology Cell biology Enzyme Activation Endothelial stem cell Cell culture Syndecan-4 Proto-Oncogene Proteins c-akt |
| Zdroj: | Molecular Cell. 32:140-149 |
| ISSN: | 1097-2765 |
| Popis: | 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 PKCalpha. Expression of myristoylated-PKCalpha in S4(-/-) cells restores rictor, mLST8, and mSin-1 presence in the rafts and rescues Akt phosphorylation. PKCalpha 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 PKCalpha to the plasma membrane is required for recruitment of mTORC2 components to the rafts and Akt activation. |
| Databáze: | OpenAIRE |
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