近日，厦门大学生命科学学院韩家淮教授课题组在《自然—细胞生物学》（Nature Cell Biology ，2009年影响因子19.527）上发表了高水平研究论文（第一作者：郑敏）。
众所周知，细胞的生长很容易受到不良环境因子抑制，然而与此类抑制相关的机制却还很不清楚。韩家淮教授课题组研究发现p38beta（MAPK11）-PRAK（p38-regulated/activated kinase）激酶级联反应与细胞低能量水平状态下mTOR（mammalian target of rapamycin）活性的抑制有关。细胞在低能量水平状态下，p38beta-PRAK激酶级联反应会被激活，被激活的PRAK通过磷酸化小G蛋白Rheb（Ras homologue enriched in brain）使其失去结合GTP的能力，从而阻断Rheb对mTORC1（mTOR Complex 1）的激活。这项研究将一个应激反应的信号通路—p38通路与控制细胞生长的信号通路—mTOR通路交联了起来，深化了人们对应激反应的认识。（生物谷Bioon.com）
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Nature Cell Biology doi:10.1038/ncb2168
Inactivation of Rheb by PRAK-mediated phosphorylation is essential for energy-depletion-induced suppression of mTORC1
Min Zheng,1 Yan-Hai Wang,1 Xiao-Nan Wu,1 Su-Qin Wu,1 Bao-Ju Lu,2 Meng-Qiu Dong,2 Hongbing Zhang,3 Peiqing Sun,4 Sheng-Cai Lin,1 Kun-Liang Guan5 & Jiahuai Han1
Cell growth can be suppressed by stressful environments, but the role of stress pathways in this process is largely unknown. Here we show that a cascade of p38β mitogen-activated protein kinase (MAPK) and p38-regulated/activated kinase (PRAK) plays a role in energy-starvation-induced suppression of mammalian target of rapamycin (mTOR), and that energy starvation activates the p38β–PRAK cascade. Depletion of p38β or PRAK diminishes the suppression of mTOR complex 1 (mTORC1) and reduction of cell size induced by energy starvation. We show that p38β–PRAK operates independently of the known mTORC1 inactivation pathways—phosphorylation of tuberous sclerosis protein 2 (TSC2) and Raptor by AMP-activated protein kinase (AMPK)—and surprisingly, that PRAK directly regulates Ras homologue enriched in brain (Rheb), a key component of the mTORC1 pathway, by phosphorylation. Phosphorylation of Rheb at Ser 130 by PRAK impairs the nucleotide-binding ability of Rheb and inhibits Rheb-mediated mTORC1 activation. The direct regulation of Rheb by PRAK integrates a stress pathway with the mTORC1 pathway in response to energy depletion.
