An evolutionarily conserved function of the Drosophila insulin receptor and insulin-like peptides in growth control
An evolutionarily conserved function of the Drosophila insulin receptor and insulin-like peptides in growth control
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DOI：
10.1016/s0960-9822(01)00068-9
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发表时间：
2001-02-20
期刊：
影响因子：
9.2
通讯作者：
Hafen, E
中科院分区：
文献类型：
--
作者：
Brogiolo, W;Stocker, H;Hafen, E
背景：尺寸调节对于开发多细胞生物的基础是基础，并通过控制细胞数和细胞大小而发生。果蝇中的研究已经确定了一种调节有机体大小的进化保守的信号通路，其中包括果蝇胰岛素受体底物同型奇科，脂质激酶P1（3）K（dp110），dakt1/dpkb和DS6K.Results：我们证明果蝇胰岛素受体同源物（DINR）的活性开发通过细胞自主方式改变细胞大小和细胞数来调节器官的大小。在人和果蝇胰岛素受体的激酶结构域中相应位置的氨基酸取代会导致严重的生长迟缓。此外，我们表明果蝇基因组包含七个胰岛素样基因，这些基因以高度组织和阶段的特异性模式表达。这些类似胰岛素样基因之一的过表达以DINR依赖性的方式改变了生长控制。结论：本研究表明，果蝇胰岛素受体自主控制细胞和器官的大小，并且编码胰岛素样肽的基因过表达足够增加体型。
Background: Size regulation is fundamental in developing multicellular organisms and occurs through the control of cell number and cell size. Studies in Drosophila have identified an evolutionarily conserved signaling pathway that regulates organismal size and that includes the Drosophila insulin receptor substrate homolog Chico, the lipid kinase P1(3)K (Dp110), DAkt1/dPKB, and dS6K.Results: We demonstrate that varying the activity of the Drosophila insulin receptor homolog (DInr) during development regulates organ size by changing cell size and cell number in a cell-autonomous manner. An amino acid substitution at the corresponding position in the kinase domain of the human and Drosophila insulin receptors causes severe growth retardation. Furthermore, we show that the Drosophila genome contains seven insulin-like genes that are expressed in a highly tissue- and stage-specific pattern. Overexpression of one of these insulin-like genes alters growth control in a DInr-dependent manner.Conclusions: This study shows that the Drosophila insulin receptor autonomously controls cell and organ size, and that overexpression of a gene encoding an insulin-like peptide is sufficient to increase body size.