Inactivation of Rheb by PRAK-mediated phosphorylation is essential for energy-depletion-induced suppression of mTORC1

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	Inactivation of Rheb by PRAK-mediated phosphorylation is essential for energy-depletion-induced suppression of mTORC1
	Zheng, M ; Wang, YH ; Wu, XN ; Wu, SQ ; Lu, BJ ; Dong, MQ ; Zhang, HB ; Sun, PQ ; Lin, SC ; Guan, KL ; Han, JH ; Han JH(韩家淮)
刊名	http://dx.doi.org/10.1038/ncb2168
	2011-03
关键词	P38 MAP-KINASES ACTIVATED PROTEIN-KINASES SMALL GTPASE RHEB CELL-GROWTH TUMOR SUPPRESSION DIRECT TARGET AMINO-ACIDS STRESS PATHWAY COMPLEX
英文摘要	NSF China [30830092, 30921005, 30828219]; 973 program [2009CB22200]; National Institutes of Health [AI41637, AI68896]; 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 p38 beta 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 p38 beta-PRAK cascade. Depletion of p38 beta or PRAK diminishes the suppression of mTOR complex 1 (mTORC1) and reduction of cell size induced by energy starvation. We show that p38 beta-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.
语种	英语
内容类型	期刊论文
源URL	[http://dspace.xmu.edu.cn/handle/2288/65866]
专题	生命科学－已发表论文
推荐引用方式 GB/T 7714	Zheng, M,Wang, YH,Wu, XN,et al. Inactivation of Rheb by PRAK-mediated phosphorylation is essential for energy-depletion-induced suppression of mTORC1[J]. http://dx.doi.org/10.1038/ncb2168,2011.
APA	Zheng, M.,Wang, YH.,Wu, XN.,Wu, SQ.,Lu, BJ.,...&韩家淮.(2011).Inactivation of Rheb by PRAK-mediated phosphorylation is essential for energy-depletion-induced suppression of mTORC1.http://dx.doi.org/10.1038/ncb2168.
MLA	Zheng, M,et al."Inactivation of Rheb by PRAK-mediated phosphorylation is essential for energy-depletion-induced suppression of mTORC1".http://dx.doi.org/10.1038/ncb2168 (2011).