Dann Stephen G, Selvaraj Anand, Thomas George
Genome Research Institute, University of Cincinnati, 2180 E. Galbraith Road, Cincinnati, OH 45237, USA.
Trends Mol Med. 2007 Jun;13(6):252-9. doi: 10.1016/j.molmed.2007.04.002. Epub 2007 Apr 23.
Recent studies demonstrate that the mammalian target of rapamycin (mTOR) and its effector, S6 kinase 1 (S6K1), lie at the crossroads of a nutrient-hormonal signaling network that is involved in specific pathological responses, including obesity, diabetes and cancer. mTOR exists in two complexes: mTOR Complex1, which is rapamycin-sensitive and phosphorylates S6K1 and initiation factor 4E binding proteins (4E-BPs), and mTOR Complex2, which is rapamycin-insensitive and phosphorylates protein kinase B (PKB, also known as Akt). Both mTOR complexes are stimulated by mitogens, but only mTOR Complex1 is under the control of nutrient and energy inputs. Thus, to orchestrate the control of homeostatic responses, mTOR Complex1 must integrate signals from distinct cues. Here, we review recent findings concerning the regulation and pathophysiology associated with mTOR Complex1 and S6K1.
近期研究表明，雷帕霉素哺乳动物靶蛋白（mTOR）及其效应分子S6激酶1（S6K1）处于一个营养-激素信号网络的交叉点，该网络参与特定的病理反应，包括肥胖、糖尿病和癌症。mTOR存在于两种复合物中：对雷帕霉素敏感的mTOR复合物1，它可磷酸化S6K1和起始因子4E结合蛋白（4E-BPs）；以及对雷帕霉素不敏感的mTOR复合物2，它可磷酸化蛋白激酶B（PKB，也称为Akt）。两种mTOR复合物均受有丝分裂原刺激，但只有mTOR复合物1受营养和能量输入的调控。因此，为协调稳态反应的控制，mTOR复合物1必须整合来自不同信号的信号。在此，我们综述了近期有关mTOR复合物1和S6K1的调控及病理生理学的研究发现。
