Interaction of Wnt and a frizzled homologue triggers G-protein-linked phosphatidylinositol signalling
Interaction of Wnt and a frizzled homologue triggers G-protein-linked phosphatidylinositol signalling
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作者：
Slusarski, DC;Corces, VG;Moon, RT
在果蝇中，卷曲组织极性基因家族的成员编码的蛋白质可能作为细胞表面受体（称为Wnt受体）发挥作用，并启动跨细胞膜的信号转导（1，2），尽管它们如何做到这一点尚不清楚。我们在这里表明，大鼠蛋白Frizzled-2导致细胞内钙的释放增加，这是由Wnt家族的成员Xwnt-5a增强。这种细胞内钙的释放受到肌醇单磷酸酶抑制剂的抑制，因此也受到磷脂酰肌醇信号通路抑制剂的抑制;这种抑制可以通过注射化合物肌醇来挽救，这克服了抑制剂引起的中间产物的减少。抑制特异性G蛋白亚基、百日咳毒素、GDP-β-S和α-转导蛋白的试剂也抑制由Xwnt-5a和大鼠Frizzled-2触发的钙释放。我们的研究结果表明，一些Wnt蛋白的工作通过特定的卷曲同源物刺激磷脂酰肌醇信号通路通过异源三聚体G蛋白亚基。
In Drosophila, members of the frizzled family of tissue-polarity genes encode proteins that are likely to function as cell-surface receptors of the type known as Wnt receptors, and to initiate signal transduction across the cell membrane(1,2), although how they do this is unclear. We show here that the rat protein Frizzled-2 causes an increase in the release of intracellular calcium which is enhanced by Xwnt-5a, a member of the Wnt family. This release of intracellular calcium is suppressed by an inhibitor of the enzyme inositol monophosphatase and hence of the phosphatidylinositol signalling pathway; this suppression can be rescued by injection of the compound myo-inositol, which overcomes the decrease in this intermediate caused by the inhibitor. Agents that inhibit specific G-protein subunits, pertussis toxin, GDP-beta-S and alpha-transducin also inhibit the calcium release triggered by Xwnt-5a and rat Frizzled-2. Our results indicate that some Wnt proteins work through specific Frizzled homologues to stimulate the phosphatidylinositol signalling pathway via heterotrimeric G-protein subunits.