Ras1 (Ras85D) and Ras2 (Ras64B) are the Drosophila orthologs of human H-Ras/N-Ras/K-Ras and R-Ras1-3 genes, respectively. The function of Ras1 has been thoroughly characterised during Drosophila embryonic and imaginal development, and it is associated with coupling activated trans-membrane receptors with tyrosine kinase activity to their downstream effectors. In this capacity, Ras1 binds and is required for the activation of Raf. Ras1 can also interact with PI3K, and it is needed to achieve maximal levels of PI3K signalling in specific cellular settings. In contrast, the function of the unique Drosophila R-Ras member (Ras2/Ras64B), which is more closely related to vertebrate R-Ras2/TC21, has been only studied through the use of constitutively activated forms of the protein. This pioneering work identified a variety of phenotypes that were related to those displayed by Ras1, suggesting that Ras1 and Ras2 might have overlapping activities. Here we find that Ras2 can interact with PI3K and Raf and activate their downstream effectors Akt and Erk. However, and in contrast to mutants in Ras1, which are lethal, null alleles of Ras2 are viable in homozygosis and only show a phenotype of reduced wing size and extended life span that might be related to reduced Insulin receptor signalling.

中文翻译：

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Ras2是TC21 / R-Ras2果蝇的同源物，有助于胰岛素信号传导，但不是有机体生存力所必需的。

Ras1（Ras85D）和Ras2（Ras64B）分别是人类H-Ras / N-Ras / K-Ras和R-Ras1-3基因的果蝇直系同源物。Ras1的功能已在果蝇的胚胎和想象的发展过程中被彻底表征，并且它与具有酪氨酸激酶活性的活化跨膜受体与其下游效应子偶联有关。Ras1以此身份绑定，并且是Raf激活所必需的。Ras1也可以与PI3K相互作用，需要在特定的细胞环境中实现PI3K信号的最大水平。相反，仅通过使用组成型活化形式的蛋白质研究了与果蝇R-Ras2 / TC21更紧密相关的独特果蝇R-Ras成员（Ras2 / Ras64B）的功能。这项开创性工作确定了与Ras1展示的表型相关的多种表型，这表明Ras1和Ras2可能具有重叠的活动。在这里，我们发现Ras2可以与PI3K和Raf相互作用并激活其下游效应子Akt和Erk。然而，与具有致命性的Ras1突变体相反，Ras2的无效等位基因在纯合中是可行的，并且仅显示出机翼尺寸减小和寿命延长的表型，这可能与胰岛素受体信号转导减少有关。