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首页> 美国卫生研究院文献>Genetics >A mutational analysis of dishevelled in Drosophila defines novel domains in the dishevelled protein as well as novel suppressing alleles of axin.
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A mutational analysis of dishevelled in Drosophila defines novel domains in the dishevelled protein as well as novel suppressing alleles of axin.

机译：果蝇中衣衫不整的突变分析定义了衣衫不整蛋白质中的新结构域以及毒素的新抑制性等位基因。

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Drosophila dishevelled (dsh) functions in two pathways: it is necessary to transduce Wingless (Wg) signaling and it is required in planar cell polarity. To learn more about how Dsh can discriminate between these functions, we performed genetic screens to isolate additional dsh alleles and we examined the potential role of protein phosphorylation by site-directed mutagenesis. We identified two alleles with point mutations in the Dsh DEP domain that specifically disrupt planar polarity signaling. When positioned in the structure of the DEP domain, these mutations are located close to each other and to a previously identified planar polarity mutation. In addition to the requirement for the DEP domain, we found that a cluster of potential phosphorylation sites in a binding domain for the protein kinase PAR-1 is also essential for planar polarity signaling. To identify regions of dsh that are necessary for Wg signaling, we screened for mutations that modified a GMR-GAL4;UAS-dsh overexpression phenotype in the eye. We recovered many alleles of the transgene containing missense mutations, including mutations in the DIX domain and in the DEP domain, the latter group mapping separately from the planar polarity mutations. In addition, several transgenes had mutations within a domain containing a consensus sequence for an SH3-binding protein. We also recovered second-site-suppressing mutations in axin, mapping at a region that may specifically interact with overexpressed Dsh.
机译：果蝇披覆（dsh）的功能通过两个途径进行：有必要转导无翅（Wg）信号，并且在平面细胞极性中也是必需的。要了解有关Dsh如何区分这些功能的更多信息，我们进行了基因筛选以分离其他dsh等位基因，并通过定点诱变研究了蛋白质磷酸化的潜在作用。我们确定了两个Dsh DEP域中具有点突变的等位基因，这些突变特异性地破坏了平面极性信号。当位于DEP结构域的结构中时，这些突变彼此靠​​近且与先前确定的平面极性突变相邻。除了对DEP域的要求外，我们发现蛋白激酶PAR-1的结合域中潜在的磷酸化位点簇对于平面极性信号也必不可少。为了识别Wg信号所必需的dsh区域，我们筛选了修饰眼睛中GMR-GAL4; UAS-dsh过表达表型的突变。我们回收了包含错义突变的转基因的许多等位基因，包括DIX域和DEP域中的突变，后一组与平面极性突变分开映射。另外，一些转基因在包含SH3结合蛋白的共有序列的结构域内具有突变。我们还恢复了毒素中第二位点抑制的突变，定位在可能与过表达的Dsh特异性相互作用的区域。

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