IR and insulin-like growth factor-1 receptor (IGF-1R) share high degree of sequence and structural similarity that hinders the development of anticancer drugs targeting IGF1R, which is dysregulated in many cancers. Although IR and IGF1R mediate their activities through similar signalling pathways, yet they show different physiological effects. The exact molecular mechanism(s) how IR and IGF1R exert their distinct functions remain largely unknown. Here, we performed in silico analysis and generated GFP-fusion proteins of wild type IR and its K1079R mutant to analyze their subcellular localization, cytoplasmic and nuclear activities in comparison to IGF1R and its K1055R mutant. We showed that, like K1055R mutation in IGF1R, K1079R mutation does not impede the subcellular localization and nuclear activities of IR. Although K1079R mutation significantly decreases the kinase activity of IR but not as much as K1055R mutation, which was seen to drastically reduce the kinase activity of IGF1R. Moreover, K1079 residue in IR is seen to be sitting in a pocket which is different than the allosteric inhibitor binding pocket present in its homologue (IGF1R). This is for the first time such a study has been conducted to identify structural differences between these receptors that could be exploited for designing small molecule allosteric inhibitor(s) of IGF1R as novel anti-cancer drugs

IR 和胰岛素样生长因子-1 受体 (IGF-1R) 具有高度的序列和结构相似性，这阻碍了针对 IGF1R 的抗癌药物的开发，IGF1R 在许多癌症中失调。虽然IR和IGF1R通过相似的信号通路介导它们的活动，但它们表现出不同的生理效应。IR 和 IGF1R 如何发挥其独特功能的确切分子机制在很大程度上仍然未知。在这里，我们在计算机上执行分析并生成野生型 IR 及其 K1079R 突变体的 GFP 融合蛋白，以分析与 IGF1R 及其 K1055R 突变体相比的亚细胞定位、细胞质和核活性。我们表明，与 IGF1R 中的 K1055R 突变一样，K1079R 突变不会阻碍 IR 的亚细胞定位和核活性。虽然 K1079R 突变显着降低了 IR 的激酶活性，但不如 K1055R 突变，后者被认为显着降低了 IGF1R 的激酶活性。此外，观察到 IR 中的 K1079 残基位于与其同系物 (IGF1R) 中存在的变构抑制剂结合口袋不同的口袋中。