Taouis M, Taylor S I, Reitman M
Institut National de la Recherche Agronomique, Station de Recherches Avicoles, Nouzilly, France.
Gene. 1996 Oct 31;178(1-2):51-5. doi: 10.1016/0378-1119(96)00333-2.
The action of insulin, IGF-1, and IGF-2 is mediated via two receptor tyrosine kinases, the insulin and IGF-1 receptors. Upon ligand binding, these receptors become active kinases, undergoing autophosphorylation and phosphorylating cellular substrates, including insulin receptor substrate-1 (IRS-1). IRS-1 acts as a docking protein and mediates multiple interactions among other proteins, resulting in transduction of the metabolic and mitogenic signals. The IRS-1 gene has been cloned from four species (human, rat, mouse, and frog). In the present study, the chicken IRS-1 gene was cloned. Chicken, as is true of birds in general, have a higher fasting and fed blood glucose than do mammals. Chicken IRS-1 DNA sequence encodes a 1240 amino acid protein. The most conserved regions were the IRS homology-2 (IH-2), the pleckstrin homology, and the shc and IRS-1 NPXY-binding (SAIN) domains. Twelve of the cIRS-1 tyrosine residues are in sequence motifs that, when phosphorylated, could interact with proteins containing SH2 domains. All twelve of these motifs were conserved. IRS-1 mRNA is expressed during embryogenesis in chicken and persists after hatching. In LMH cells, derived from a chicken hepatoma, two bands were tyrosine phosphorylated in an insulin-dependent manner: IRS-1 (approximately 180 kDa) and the insulin receptor beta subunit (approximately 95 kDa). Chicken IRS-1 is structurally and functionally similar to its human homolog, despite the difference in blood glucose levels and the evolutionary distance between birds and mammals.
胰岛素、胰岛素样生长因子-1（IGF-1）和胰岛素样生长因子-2（IGF-2）的作用是通过两种受体酪氨酸激酶介导的，即胰岛素受体和IGF-1受体。配体结合后，这些受体成为活性激酶，进行自身磷酸化并磷酸化细胞底物，包括胰岛素受体底物-1（IRS-1）。IRS-1作为一种对接蛋白，介导与其他蛋白质之间的多种相互作用，从而导致代谢和促有丝分裂信号的转导。IRS-1基因已从四种物种（人类、大鼠、小鼠和青蛙）中克隆出来。在本研究中，克隆了鸡的IRS-1基因。与一般鸟类一样，鸡的空腹和进食后血糖水平高于哺乳动物。鸡IRS-1的DNA序列编码一种含1240个氨基酸的蛋白质。最保守的区域是IRS同源性-2（IH-2）、普列克底物蛋白同源性以及shc和IRS-1 NPXY结合（SAIN）结构域。cIRS-1的12个酪氨酸残基位于序列基序中，磷酸化后可与含SH2结构域的蛋白质相互作用。所有这12个基序都是保守的。IRS-1 mRNA在鸡胚胎发育过程中表达，并在孵化后持续存在。在源自鸡肝癌的LMH细胞中，两条带以胰岛素依赖的方式发生酪氨酸磷酸化：IRS-1（约180 kDa）和胰岛素受体β亚基（约95 kDa）。尽管鸡和哺乳动物的血糖水平存在差异，且在进化上相距甚远，但鸡IRS-1在结构和功能上与其人类同源物相似。
