Casein kinase 1 controls components of a TORC2 signaling network in budding yeast.
Casein kinase 1 controls components of a TORC2 signaling network in budding yeast.
复制标题
酪蛋白激酶 1 控制芽殖酵母中 TORC2 信号网络的组成部分。
DOI：
10.1101/2024.01.30.578072
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发表时间：
2024
期刊：
影响因子：
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通讯作者：
Alcaide-Gavilan,Maria
中科院分区：
文献类型：
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作者：
Lucena,Rafael;Jasani,Akshi;Anastasia,Steph;Kellogg,Douglas;Alcaide-Gavilan,Maria
Tor激酶在控制营养信号传导和细胞生长中发挥着多种重要作用。这些激酶被组装成两个多蛋白复合物TORC1和TORC2。在出芽酵母中，TORC2传递营养依赖信号，强烈影响生长速度和细胞大小。然而，人们对控制TORC2信号的机制知之甚少。TORC2的激活需要Mss4，一种招募和激活TORC2下游靶点的磷脂酰肌醇4-磷酸5激酶。Mss4在质膜上的定位被认为是由磷酸化控制的，以前的研究表明酵母同源的酪蛋白激酶1、Yck1和Yck2（这里统称为Yck1/2）控制着Mss4的磷酸化。在这里，我们生成了一个新的YCK2类似物敏感等位基因，并使用它来测试Yck1/2是否影响Mss4的定位或TORC2网络中的信号传导。我们发现Yck1/2强烈影响Mss4磷酸化和定位，并影响TORC2网络多个组分的调控。然而，抑制Yck1/2会对TORC2通路中最具特征的信号轴产生轻微影响，这表明Yck1/2可能在影响TORC2信号传导的不太为人所知的方面发挥更大的作用。
Tor kinases play diverse and essential roles in control of nutrient signaling and cell growth. These kinases are assembled into two multiprotein complexes known as TORC1 and TORC2. In budding yeast, TORC2 relays nutrient-dependent signals that strongly influence growth rate and cell size. However, the mechanisms that control TORC2 signaling are poorly understood. Activation of TORC2 requires Mss4, a phosphatidylinositol 4-phosphate 5-kinase that recruits and activates downstream targets of TORC2. Localization of Mss4 to the plasma membrane is thought to be controlled by phosphorylation, and previous work has suggested that yeast homologs of casein kinase 1, Yck1 and Yck2 (referred to here collectively as Yck1/2), Control phosphorylation of Mss4. Here, we generated a new analog-sensitive allele of YCK2 and used it to test whether Yck1/2 influence localization of Mss4 or signaling in the TORC2 network. We found that Yck1/2 strongly influence Mss4 phosphorylation and localization, as well as influencing regulation of multiple components of the TORC2 network. However, inhibition of Yck1/2 causes mild effects on the best-characterized signaling axis in the TORC2 pathway, suggesting that Yck1/2 might play a larger role in influencing less well-understood aspects of TORC2 signaling.