Vertebrate proteins related to Drosophila naked cuticle bind dishevelled and antagonize Wnt signaling
Vertebrate proteins related to Drosophila naked cuticle bind dishevelled and antagonize Wnt signaling
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DOI：
10.1006/dbio.2001.0238
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发表时间：
2001-06-01
影响因子：
2.7
通讯作者：
Scott, MP
中科院分区：
文献类型：
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作者：
Wharton, KA;Zimmermann, G;Scott, MP
在后生动物中，Wnt信号控制细胞命运决定并协调细胞行为。在果蝇Drosophila中，由Wnt蛋白Wingless（Wg）介导的信号传导缺陷的胚胎表现出严重的分割缺陷。果蝇节极性基因裸角质层（nkd）编码的EF手蛋白，调节早期Wg活动作为一种诱导型拮抗剂。Nkd通过与Wnt信号传导组分Dishevelled（Dsh）的直接相互作用拮抗Wg。在这里，我们描述了两个小鼠和人类的蛋白质，Nkd 1和Nkd 2，相关的苍蝇Nkd。果蝇和脊椎动物蛋白中最保守的区域，EFX结构域，包括推定的EE手和侧翼序列。EFX对应于在酵母双杂交测定中果蝇或脊椎动物Nkd与果蝇Dsh或脊椎动物Dvl蛋白的碱性/PDZ结构域相互作用所需的最小结构域。在小鼠发育过程中，nkd 1和nkd 2在多个组织中以部分重叠的梯度样模式表达，其中一些与已知的Wnt活性模式相关。小鼠Nkd 1可以阻断Wnt 1介导的，但不是β-连环蛋白介导的，哺乳动物细胞培养物中Wnt依赖性报告构建体的激活。小鼠nkd 1在果蝇中的错误表达拮抗Wg功能。这些数据表明，脊椎动物Nkd相关蛋白，类似于它们的苍蝇对应物，可以作为Wnt信号的诱导型拮抗剂。(C)北京：科学出版社.
Wnt signals control cell fate decisions and orchestrate cell behavior in metazoan animals. In the fruit fly Drosophila, embryos defective in signaling mediated by the Wnt protein Wingless (Wg) exhibit severe segmentation defects. The Drosophila segment polarity gene naked cuticle (nkd) encodes an EF hand protein that regulates early Wg activity by acting as an inducible antagonist. Nkd antagonizes Wg via a direct interaction with the Wnt signaling component Dishevelled (Dsh). Here we describe two mouse and human proteins, Nkd1 and Nkd2, related to fly Nkd. The most conserved region among the fly and vertebrate proteins, the EFX domain, includes the putative EE hand and flanking sequences. EFX corresponds to a minimal domain required for fly or vertebrate Nkd to interact with the basic/PDZ domains of fly Dsh or vertebrate Dvl proteins in the yeast two-hybrid assay. During mouse development, nkd1 and nkd2 are expressed in multiple tissues in partially overlapping, gradient-like patterns, some of which correlate with known patterns of Wnt activity. Mouse Nkd1 can block Wnt1-mediated, but not beta -catenin-mediated, activation of a Wnt-dependent reporter construct in mammalian cell culture. Misexpression of mouse nkd1 in Drosophila antagonizes Wg function. The data suggest that the vertebrate Nkd-related proteins, similar to their fly counterpart, may act as inducible antagonists of Wnt signals. (C) 2001 Academic Press.