TORC2在蛋白激酶C（PKC）和Akt转角基序磷酸化、成熟及信号传导中的重要功能。
Essential function of TORC2 in PKC and Akt turn motif phosphorylation, maturation and signalling.
作者信息
Ikenoue Tsuneo, Inoki Ken, Yang Qian, Zhou Xiaoming, Guan Kun-Liang
机构信息
Life Sciences Institute, University of Michigan, Ann Arbor, MI, USA.
出版信息
EMBO J. 2008 Jul 23;27(14):1919-31. doi: 10.1038/emboj.2008.119. Epub 2008 Jun 19.
Abstract
Protein kinase C (PKC) is involved in a wide array of cellular processes such as cell proliferation, differentiation and apoptosis. Phosphorylation of both turn motif (TM) and hydrophobic motif (HM) are important for PKC function. Here, we show that the mammalian target of rapamycin complex 2 (mTORC2) has an important function in phosphorylation of both TM and HM in all conventional PKCs, novel PKCepsilon as well as Akt. Ablation of mTORC2 components (Rictor, Sin1 or mTOR) abolished phosphorylation on the TM of both PKCalpha and Akt and HM of Akt and decreased HM phosphorylation of PKCalpha. Interestingly, the mTORC2-dependent TM phosphorylation is essential for PKCalpha maturation, stability and signalling. Our study demonstrates that mTORC2 is involved in post-translational processing of PKC by facilitating TM and HM phosphorylation and reveals a novel function of mTORC2 in cellular regulation.
摘要
蛋白激酶C（PKC）参与多种细胞过程，如细胞增殖、分化和凋亡。转角基序（TM）和疏水基序（HM）的磷酸化对PKC功能都很重要。在此，我们表明雷帕霉素复合物2（mTORC2）的哺乳动物靶点在所有传统PKC、新型PKCε以及Akt的TM和HM磷酸化中具有重要作用。mTORC2组分（Rictor、Sin1或mTOR）的缺失消除了PKCα和Akt的TM以及Akt的HM上的磷酸化，并降低了PKCα的HM磷酸化。有趣的是，mTORC2依赖性的TM磷酸化对于PKCα的成熟、稳定性和信号传导至关重要。我们的研究表明，mTORC2通过促进TM和HM磷酸化参与PKC的翻译后加工，并揭示了mTORC2在细胞调节中的新功能。
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