- 作者：Takako Kikuchi ; Jun Zhang ; Hideyuki Sakoda ; Yuko Koketsu ; Midori Fujishiro ; Akifumi Kushiyama ; Yusuke Nakatsu ; Hideaki Kamata ; Ken Inoki ; Shin-Ichiro Takahashi ; Hiroki Kurihara ; Katagiri Hideki ; Yoshitomo Oka ; Tomoichiro Asano
- 关键词：mTOR ; LST8 ; Raptor ; Rictor
- 刊名：Obesity Research Clinical Practice
- 出版年：2012
- 出版时间：July-September, 2012
- 年：2012
- 卷：6
- 期：3
- 页码：e215-e224
- 全文大小：759 K
Summary
LST8 is a component of both mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). Herein, to examine the role of LST8, a common component of mTOR complexes, in the regulation of mTORC1 and mTORC2, first, we showed over-expression of LST8 in HepG2 to markedly enhance basal phosphorylation levels of not only p70 S6 kinase but also Akt. In contrast, LST8 knockdown by siRNA in HepG2 decreased phosphorylation levels of both p70 S6 kinase and Akt. These results indicate the LST8 expression level to determine basal mTORC1 and mTORC2 activities, since LST8 appears to be the component present at the lowest level in both mTORC1 and mTORC2 complexes.Previously, we reported S6 kinase phosphorylation to be reduced by over-expression of the Cterminally deleted Raptor mutant (Raptor-¦¤CT) not binding to mTOR or LST8, while phosphorylation levels of Akt were markedly enhanced with no alteration in IRS-1 phosphorylation or PI 3-kinase activity. Using Raptor-¦¤CT, we investigated the competition for association with LST8 between mTORC1 and mTORC2. Over-expression of Raptor-¦¤CT abolished formation of the Raptor, S6 kinase, mTOR and LST8 complex, while the amount of LST8 in the Rictor-mTOR complex was increased. Therefore, it is likely that Raptor-mTOR and Rictor-mTOR complexes compete for association with LST8, and this mechanism may contribute to the reciprocal negative regulations of mTORC1 and mTORC2 activities, in terms of their LST8 components.