Gene interactions and pathways from curated databases and text-mining
Mol Cell 2008, PMID: 18851840

Syndecan-4 regulates subcellular localization of mTOR Complex2 and Akt activation in a PKCalpha-dependent manner in endothelial cells.

Partovian, Chohreh; Ju, Rong; Zhuang, Zhen W; Martin, Kathleen A; Simons, Michael

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.

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Text Mining Data

Akt → Syndecan-4: " Syndecan-4 regulates subcellular localization of mTOR Complex2 and Akt activation in a PKCalpha dependent manner in endothelial cells "

Syndecan-4 — PKCalpha: " Syndecan-4 regulates subcellular localization of mTOR Complex2 and Akt activation in a PKCalpha dependent manner in endothelial cells "

Akt — PKCalpha: " Syndecan-4 regulates subcellular localization of mTOR Complex2 and Akt activation in a PKCalpha dependent manner in endothelial cells "

FoxO1/3a ⊣ mTORC2: " 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 "

eNOS ⊣ mTORC2: " 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 "

Manually curated Databases

No curated data.