Yeast can accommodate phosphotyrosine: v-Src toxicity in yeast arises from a single disrupted pathway.
Yeast can accommodate phosphotyrosine: v-Src toxicity in yeast arises from a single disrupted pathway.
复制标题
酵母可以容纳磷酸酪氨酸：酵母中的 v-Src 毒性来自于单一被破坏的途径。
DOI：
10.1093/femsyr/foy027
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发表时间：
2018
影响因子：
3.2
通讯作者：
Lindquist,Susan
中科院分区：
文献类型：
--
作者：
Kritzer,JoshuaA;Freyzon,Yelena;Lindquist,Susan
酪氨酸磷酸化是控制多细胞生物生长和分化的关键生化信号，酵母和几乎所有其他单细胞真核生物都缺乏完整的酪氨酸磷酸化信号通路。然而，这些生物体中的许多具有原始的磷酸酪氨酸结合蛋白和酪氨酸磷酸酶，导致假设磷酸酪氨酸信号传导出现的主要障碍是混杂酪氨酸激酶活性的负面后果。在这项工作中，我们揭示了经典的致癌基因v-Src，它磷酸化酵母中的许多蛋白质，是有毒的，因为它破坏了一个特定的孢子壁重塑途径。使用遗传选择，我们发现，一个特定的环肽的表达，或过度表达的SMK 1，MAP激酶，控制孢子壁组装，都导致强劲的增长，尽管在酵母蛋白质组中的磷酸酪氨酸的连续高水平。因此，最小的遗传操作允许酵母耐受高水平的磷酸酪氨酸。这些结果表明，在单细胞生物体中引入酪氨酸激酶可能不是磷酸酪氨酸信号进化的主要障碍。
Tyrosine phosphorylation is a key biochemical signal that controls growth and differentiation in multicellular organisms.Saccharomyces cerevisiaeand nearly all other unicellular eukaryotes lack intact phosphotyrosine signaling pathways. However, many of these organisms have primitive phosphotyrosine-binding proteins and tyrosine phosphatases, leading to the assumption that the major barrier for emergence of phosphotyrosine signaling was the negative consequences of promiscuous tyrosine kinase activity. In this work, we reveal that the classic oncogene v-Src, which phosphorylates many dozens of proteins in yeast, is toxic because it disrupts a specific spore wall remodeling pathway. Using genetic selections, we find that expression of a specific cyclic peptide, or overexpression ofSMK1, a MAP kinase that controls spore wall assembly, both lead to robust growth despite a continuous high level of phosphotyrosine in the yeast proteome. Thus, minimal genetic manipulations allow yeast to tolerate high levels of phosphotyrosine. These results indicate that the introduction of tyrosine kinases within single-celled organisms may not have been a major obstacle to the evolution of phosphotyrosine signaling.