Yonezawa Kazuyoshi, Tokunaga Chiharu, Oshiro Noriko, Yoshino Ken-ichi
Biosignal Research Center, Kobe University, Kobe 657-8501, Japan.
Biochem Biophys Res Commun. 2004 Jan 9;313(2):437-41. doi: 10.1016/j.bbrc.2003.07.018.
The mammalian target of rapamycin (mTOR) controls cell growth in response to amino acids and growth factors, in part by regulating p70 S6 kinase alpha (p70 alpha) and eukaryotic initiation factor 4E binding protein 1 (4EBP1). Raptor (regulatory associated protein of mTOR) is a 150 kDa mTOR binding protein that is essential for TOR signaling in vivo and also binds 4EBP1 and p70alpha through their respective TOS (TOR signaling) motifs, a short conserved segment previously shown to be required for amino acid- and mTOR-dependent regulation of these substrates in vivo. Raptor appears to serve as an mTOR scaffold protein, the binding of which to the TOS motif of mTOR substrates is necessary for effective mTOR-catalyzed phosphorylation. Further understanding of regulation of the mTOR-raptor complex in response to the nutritional environment would require identification of the interplay between the mTOR-raptor complex and its upstream effectors such as the protein products of tumor suppressor gene tuberous sclerosis complexes 1 and 2, and the Ras-related small G protein Rheb.
雷帕霉素哺乳动物靶点(mTOR)通过部分调节p70 S6激酶α(p70α)和真核起始因子4E结合蛋白1(4EBP1)来控制细胞对氨基酸和生长因子的生长反应。Raptor(mTOR调节相关蛋白)是一种150 kDa的mTOR结合蛋白,对体内TOR信号传导至关重要,并且还通过其各自的TOS(TOR信号传导)基序结合4EBP1和p70α,这是一个短的保守片段,先前已证明在体内对这些底物进行氨基酸和mTOR依赖性调节是必需的。Raptor似乎作为一种mTOR支架蛋白,其与mTOR底物的TOS基序结合对于有效的mTOR催化磷酸化是必要的。要进一步了解mTOR-Raptor复合物对营养环境的反应调节,需要确定mTOR-Raptor复合物与其上游效应器之间的相互作用,例如肿瘤抑制基因结节性硬化复合物1和2的蛋白质产物,以及Ras相关小G蛋白Rheb。