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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >TSC1/TSC2 and Rheb have different effects on TORC1 and TORC2 activity
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TSC1/TSC2 and Rheb have different effects on TORC1 and TORC2 activity

机译：TSC1 / TSC2和Rheb对TORC1和TORC2活性的影响不同

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Target of rapamycin (TOR) plays a central role in cell growth regulation by integrating signals from growth factors, nutrients, and cellular energy levels. TOR forms two distinct physical and functional complexes, termed TOR complex 1 (TORC1) and TOR complex 2 (TORC2). TORC1, which is sensitive to rapamycin, regulates translation and cell growth, whereas TORC2, which is insensitive to rapamycin, regulates cell morphology and cell growth. The Ras homology enriched in brain (Rheb) small GTPase is known to be a key upstream activator of TORC1, although the mechanism of Rheb in TORC1 activation remains to be determined. However, the function of Rheb in the TORC2 regulation has not been elucidated. By measuring Akt and S6K phosphorylation as a functional assay for TORC1 and -2, here, we report that dRheb has an inhibitory effect on dTORC2 activity in Drosophila S2 cells. This negative effect of dRheb on dTORC2 is possibly due to a feedback mechanism involving dTORC1 and dS6K. We also observed that Rheb does not activate TORC2 in human embryonic kidney 293 cells, although it potently stimulates TORC1. Furthermore, tuberous sclerosis complex 1 (TSC1) and TSC2, which are negative regulators of Rheb, have negative and positive effects on TORC1 and -2, respectively. Our observations suggest that TSC1/2 and Rheb have different effects on the activity of TORC1 and -2, further supporting the complexity of TOR regulation.
机译：雷帕霉素（TOR）的靶标通过整合来自生长因子，营养素和细胞能量水平的信号，在细胞生长调节中发挥核心作用。 TOR形成两个不同的物理和功能复合物，称为TOR复合物1（TORC1）和TOR复合物2（TORC2）。对雷帕霉素敏感的TORC1调节翻译和细胞生长，而对雷帕霉素不敏感的TORC2调节细胞形态和细胞生长。尽管Rheb在TORC1激活中的机制尚待确定，但富含脑（Rheb）小GTPase的Ras同源性是TORC1的关键上游激活因子。但是，尚未阐明Rheb在TORC2法规中的功能。通过测量Akt和S6K磷酸化作为TORC1和-2的功能测定，在这里，我们报道dRheb对果蝇S2细胞中dTORC2活性具有抑制作用。 dRheb对dTORC2的负面影响可能是由于涉及dTORC1和dS6K的反馈机制。我们还观察到Rheb虽然有效刺激TORC1，但它并未激活人胚肾293细胞中的TORC2。此外，结节性硬化复合物1（TSC1）和TSC2是Rheb的负调控因子，分别对TORC1和-2具有负作用和正作用。我们的观察结果表明，TSC1 / 2和Rheb对TORC1和-2的活性具有不同的影响，进一步支持了TOR调节的复杂性。

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