Mammalian, or mechanistic, target of rapamycin complex 2 (mTORC2) regulates a variety of vital cellular processes, and its aberrant functioning is often associated with various diseases. Rictor is a peculiar and distinguishing mTORC2 component playing a pivotal role in controlling its assembly and activity. Among extant organisms, Rictor is conserved from unicellular eukaryotes to metazoans. We replaced two distinct, but conserved, glycine residues in both the Dictyostelium piaA gene and its human ortholog, RICTOR The two conserved residues are spaced ∼50 amino acids apart, and both are embedded within a conserved region falling in between the Ras-GEFN2 and Rictor-_V domains. The effects of point mutations on the mTORC2 activity and integrity were assessed by biochemical and functional assays. In both cases, these equivalent point mutations in the mammalian RICTOR and Dictyostelium piaA gene impaired mTORC2 activity and integrity. Our data indicate that the two glycine residues are essential for the maintenance of mTORC2 activity and integrity in organisms that appear to be distantly related, suggesting that they have a evolutionarily conserved role in the assembly and proper mTORC2 functioning.

中文翻译：

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mTORC2的活性和完整性需要哺乳动物和Dictyostelium Rictor中两个保守的甘氨酸残基。

雷帕霉素复合物2（mTORC2）的哺乳动物或机械靶标可调节多种重要的细胞过程，其异常功能通常与多种疾病有关。Rictor是一种独特的mTORC2组件，在控制其装配和活动中起着举足轻重的作用。在现存的生物中，Rictor从单细胞真核生物到后生动物都是保守的。我们替换了Dictyostelium piaA基因及其人类直系同源物RICTOR中的两个截然不同但保守的甘氨酸残基。这两个保守残基彼此间隔约50个氨基酸，并且都被嵌入Ras-GEFN2和Ras-GEFN2之间的保守区域内。 Rictor-_V域。通过生化和功能分析评估了点突变对mTORC2活性和完整性的影响。在这两种情况下 哺乳动物RICTOR和Dictyostelium piaA基因中的这些等价点突变削弱了mTORC2的活性和完整性。我们的数据表明，这两个甘氨酸残基对于维持mTORC2活性和完整性似乎很远的生物体至关重要，这表明它们在装配过程中具有进化上的保守性，并能正常发挥mTORC2的功能。