TOR and PKA signaling pathways converge on the protein kinase Rim15 to control entry into G0
TOR and PKA signaling pathways converge on the protein kinase Rim15 to control entry into G0
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DOI：
10.1016/s1097-2765(03)00485-4
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发表时间：
2003-12-01
期刊：
影响因子：
16
通讯作者：
De Virgilio, C
中科院分区：
文献类型：
--
作者：
Pedruzzi, I;Dubouloz, F;De Virgilio, C
高度保守的Tor激酶（TOR）和蛋白激酶A（PKA）途径响应于生长因子和/或营养物调节细胞增殖。在酿酒酵母中，TOR或PKA的缺失导致细胞在G（1）早期停止生长，并通过尚不清楚的机制进入G（0）。在这里，我们证明了蛋白激酶Rim 15是TOR和/或PKA失活后进入G（0）所必需的。Rim 15依赖性G（0）性状的诱导需要两个独立的过程，即，Rim 15的核积累，其受Sit 4非依赖性TOR效应子分支和蛋白激酶B（PKB/Akt）同源物Sch 9的负调控，并从PKA介导的其蛋白激酶活性抑制中释放。因此，Rim 15整合了来自至少三种营养感觉激酶（TOR、PKA和Sch 9）的信号，以适当地控制进入G（0），这是真核细胞中的关键发育过程。
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.