Khayath Naji, Vicogne Jerome, Ahier Arnaud, BenYounes Amena, Konrad Christian, Trolet Jacques, Viscogliosi Eric, Brehm Klaus, Dissous Colette
U547 INSERM, Institut Pasteur de Lille, Lille Cedex, France.
FEBS J. 2007 Feb;274(3):659-76. doi: 10.1111/j.1742-4658.2006.05610.x. Epub 2006 Dec 20.
Insulin signalling is a very ancient and well conserved pathway in metazoan cells, dependent on insulin receptors (IR) which are transmembrane proteins with tyrosine kinase activity. A unique IR is usually present in invertebrates whereas two IR members are found with different functions in vertebrates. This work demonstrates the existence of two distinct IR homologs (SmIR-1 and SmIR-2) in the parasite trematode Schistosoma mansoni. These two receptors display differences in several structural motifs essential for signalling and are differentially expressed in parasite tissues, suggesting that they could have distinct functions. The gene organization of SmIR-1 and SmIR-2 is similar to that of the human IR and to that of the IR homolog from Echinococcus multilocularis (EmIR), another parasitic platyhelminth. SmIR-1 and SmIR-2 were shown to interact with human pro-insulin but not with pro-insulin-like growth factor-1 in two-hybrid assays. Phylogenetic results indicated that SmIR-2 and EmIR might be functional orthologs whereas SmIR-1 would have emerged to fulfil specific functions in schistosomes.
胰岛素信号传导是后生动物细胞中一条非常古老且保守的途径，它依赖于胰岛素受体（IR），胰岛素受体是具有酪氨酸激酶活性的跨膜蛋白。无脊椎动物中通常存在一种独特的胰岛素受体，而在脊椎动物中发现了两个具有不同功能的胰岛素受体成员。这项研究证明了在寄生虫曼氏血吸虫中存在两种不同的胰岛素受体同源物（SmIR - 1和SmIR - 2）。这两种受体在信号传导所必需的几个结构基序上存在差异，并且在寄生虫组织中的表达也不同，这表明它们可能具有不同的功能。SmIR - 1和SmIR - 2的基因结构与人类胰岛素受体以及另一种寄生扁形虫多房棘球绦虫的胰岛素受体同源物（EmIR）的基因结构相似。在双杂交实验中，SmIR - 1和SmIR - 2被证明与人胰岛素原相互作用，但不与人胰岛素样生长因子 - 1相互作用。系统发育结果表明，SmIR - 2和EmIR可能是功能直系同源物，而SmIR - 1可能是为了在血吸虫中履行特定功能而出现的。
