近日,，廈門大學生命科學學院韓家淮教授課題組在《自然—細胞生物學》（Nature Cell Biology ,，2009年影響因子19.527）上發(fā)表了高水平研究論文（第一作者：鄭敏）。
眾所周知,，細胞的生長很容易受到不良環(huán)境因子抑制,，然而與此類抑制相關(guān)的機制卻還很不清楚,。韓家淮教授課題組研究發(fā)現(xiàn)p38beta（MAPK11）-PRAK（p38-regulated/activated kinase）激酶級聯(lián)反應與細胞低能量水平狀態(tài)下mTOR（mammalian target of rapamycin）活性的抑制有關(guān),。細胞在低能量水平狀態(tài)下,，p38beta-PRAK激酶級聯(lián)反應會被激活，被激活的PRAK通過磷酸化小G蛋白Rheb（Ras homologue enriched in brain）使其失去結(jié)合GTP的能力,，從而阻斷Rheb對mTORC1（mTOR Complex 1）的激活,。這項研究將一個應激反應的信號通路—p38通路與控制細胞生長的信號通路—mTOR通路交聯(lián)了起來，深化了人們對應激反應的認識,。（生物谷Bioon.com）
生物谷推薦相關(guān)文章：
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.
