Slusarski D C, Corces V G, Moon R T
Department of Biology, The Johns Hopkins University, Baltimore, Maryland 21218, USA.
Nature. 1997 Nov 27;390(6658):410-3. doi: 10.1038/37138.
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, 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.
在果蝇中，组织极性基因的卷曲蛋白家族成员编码的蛋白质可能作为一种名为Wnt受体的细胞表面受体发挥作用，并启动跨细胞膜的信号转导，尽管其具体机制尚不清楚。我们在此表明，大鼠蛋白卷曲蛋白-2会导致细胞内钙释放增加，而Wnt家族成员Xwnt-5a可增强这种增加。细胞内钙的这种释放受到肌醇单磷酸酶（因而也是磷脂酰肌醇信号通路）抑制剂的抑制；通过注射化合物肌醇可挽救这种抑制作用，肌醇可克服抑制剂导致的该中间产物减少。抑制特定G蛋白亚基的试剂、百日咳毒素、GDP-β-S和α-转导蛋白也会抑制由Xwnt-5a和大鼠卷曲蛋白-2触发的钙释放。我们的结果表明，一些Wnt蛋白通过特定的卷曲蛋白同源物发挥作用，经由异源三聚体G蛋白亚基刺激磷脂酰肌醇信号通路。
