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TOR和PKA信号通路汇聚于蛋白激酶Rim15,以控制进入G0期。

TOR and PKA signaling pathways converge on the protein kinase Rim15 to control entry into G0.

作者信息

Pedruzzi Ivo, Dubouloz Frédérique, Cameroni Elisabetta, Wanke Valeria, Roosen Johnny, Winderickx Joris, De Virgilio Claudio

机构信息

Department of Medical Biochemistry, CMU, University of Geneva, 1211 Geneva 4, Switzerland.

出版信息

Mol Cell. 2003 Dec;12(6):1607-13. doi: 10.1016/s1097-2765(03)00485-4.

Abstract

The highly conserved Tor kinases (TOR) and the protein kinase A (PKA) pathway regulate cell proliferation in response to growth factors and/or nutrients. In Saccharomyces cerevisiae, loss of either TOR or PKA causes cells to arrest growth early in G(1) and to enter G(0) by mechanisms that are poorly understood. Here we demonstrate that the protein kinase Rim15 is required for entry into G(0) following inactivation of TOR and/or PKA. Induction of Rim15-dependent G(0) traits requires two discrete processes, i.e., nuclear accumulation of Rim15, which is negatively regulated both by a Sit4-independent TOR effector branch and the protein kinase B (PKB/Akt) homolog Sch9, and release from PKA-mediated inhibition of its protein kinase activity. Thus, Rim15 integrates signals from at least three nutrient-sensory kinases (TOR, PKA, and Sch9) to properly control entry into G(0), a key developmental process in eukaryotic cells.

摘要

高度保守的雷帕霉素靶蛋白激酶(TOR)和蛋白激酶A(PKA)信号通路可响应生长因子和/或营养物质调节细胞增殖。在酿酒酵母中,TOR或PKA的缺失会导致细胞在G1期早期停止生长,并通过尚不清楚的机制进入G0期。在这里,我们证明蛋白激酶Rim15是TOR和/或PKA失活后进入G0期所必需的。Rim15依赖性G0期特征的诱导需要两个独立的过程,即Rim15的核积累,这受到不依赖Sit4的TOR效应分支和蛋白激酶B(PKB/Akt)同源物Sch9的负调控,以及从PKA介导的对其蛋白激酶活性的抑制中释放出来。因此,Rim15整合了来自至少三种营养感应激酶(TOR、PKA和Sch9)的信号,以正确控制进入G0期,这是真核细胞中的一个关键发育过程。

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