Malbon Craig C, Wang Hsien-Yu
Department of Pharmacology, State University of New York at Stony Brook, Stony Brook, New York 11794, USA.
Curr Top Dev Biol. 2006;72:153-66. doi: 10.1016/S0070-2153(05)72002-0.
Wnt proteins are secreted glycoprotein ligands that regulate critical aspects of development, including cell proliferation, apoptosis, and cell fate. For those pathways downstream from the "canonical" Wnt/beta-catenin signaling, from the "non-canonical" or planar cell polarity (PCP), and from the Wnt-Ca(2+)/cyclic guanosine monophosphate (cGMP) pathway, Wnt activation of its cellular receptor, a member of the superfamily of G-protein-coupled receptor Frizzled family, requires both heterotrimeric G proteins and the phosphoprotein Dishevelled. Our understanding of the roles of Dishevelled proteins in development is evolving and most recent observations suggest that Dishevelled proteins act as scaffolds essential for Wnt signaling, providing docking sites for a diverse and interesting set of protein kinases, phosphatases, adaptor proteins, G proteins, and other scaffolds such as Axin. The protein-protein interactions of Dishevelled are dynamic, as is the spatial localization of this "toolbox" of signaling molecules involved in development. Much excitement awaits the elucidation of the complete set of tools in the toolbox and of the dynamic regulation of Dishevelled proteins and their interacting proteins.
Wnt蛋白是分泌型糖蛋白配体，可调节发育的关键方面，包括细胞增殖、凋亡和细胞命运。对于“经典”Wnt/β-连环蛋白信号通路、“非经典”或平面细胞极性（PCP）以及Wnt-Ca(2+)/环磷酸鸟苷（cGMP）通路的下游通路而言，Wnt激活其细胞受体（G蛋白偶联受体卷曲蛋白家族超家族的成员）既需要异源三聚体G蛋白，也需要磷蛋白散乱蛋白。我们对散乱蛋白在发育中的作用的理解正在不断发展，最近的观察表明，散乱蛋白作为Wnt信号传导所必需的支架，为各种有趣的蛋白激酶、磷酸酶、衔接蛋白、G蛋白以及其他支架（如轴蛋白）提供对接位点。散乱蛋白的蛋白质-蛋白质相互作用是动态的，参与发育的这种信号分子“工具箱”的空间定位也是如此。在阐明该工具箱中的全套工具以及散乱蛋白及其相互作用蛋白的动态调节方面，还有很多令人兴奋的事情等待着我们去发现。
