Sanford-Burnham Medical Research Institute, 10901 North Torrey Pines Road, La Jolla, CA 92307, USA.
Mol Cell. 2011 Oct 7;44(1):134-46. doi: 10.1016/j.molcel.2011.06.038.
The signaling adaptor p62 is a critical mediator of important cellular functions, owing to its ability to establish interactions with various signaling intermediaries. Here, we identify raptor as an interacting partner of p62. Thus, p62 is an integral part of the mTORC1 complex and is necessary to mediate amino acid signaling for the activation of S6K1 and 4EBP1. p62 interacts in an amino acid-dependent manner with mTOR and raptor. In addition, p62 binds the Rags proteins and favors formation of the active Rag heterodimer that is further stabilized by raptor. Interestingly, p62 colocalizes with Rags at the lysosomal compartment and is required for the interaction of mTOR with Rag GTPases in vivo and for translocation of the mTORC1 complex to the lysosome, a crucial step for mTOR activation.
信号接头蛋白 p62 是一种重要的细胞功能关键介质，这要归功于其与各种信号中介物建立相互作用的能力。在这里，我们确定了 raptor 是 p62 的一个相互作用伙伴。因此，p62 是 mTORC1 复合物的一个组成部分，对于介导氨基酸信号以激活 S6K1 和 4EBP1 是必需的。p62 以依赖于氨基酸的方式与 mTOR 和 raptor 相互作用。此外，p62 与 Rags 蛋白结合，并有利于形成活性 Rag 异二聚体，该异二聚体进一步被 raptor 稳定。有趣的是，p62 与 Rags 在溶酶体区室中共定位，并且对于 mTOR 与 Rag GTPases 在体内的相互作用以及 mTORC1 复合物向溶酶体的易位是必需的，这是 mTOR 激活的关键步骤。
