All Dact (Dapper/Frodo) scaffold proteins dimerize and exhibit conserved interactions with Vangl, Dvl, and serine/threonine kinases.
All Dact (Dapper/Frodo) scaffold proteins dimerize and exhibit conserved interactions with Vangl, Dvl, and serine/threonine kinases.
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DOI：
10.1186/1471-2091-12-33
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发表时间：
2011-06-30
期刊：
影响因子：
--
通讯作者：
Cheyette BN
中科院分区：
文献类型：
--
作者：
Kivimäe S;Yang XY;Cheyette BN
支架蛋白的Dact家族是通过与Wnt和平面细胞极性（PCP）信号传导中心的Dvl蛋白结合而发现的。随后，Dact蛋白已经与越来越多的潜在伴侣相关联，这些潜在伴侣涉及Wnt和其他信号传导的β-连环蛋白依赖性和β-连环蛋白非依赖性形式。为了澄清保守和非保守的作用，这个蛋白质家族，我们系统地比较了所有三个小鼠Dact旁系同源物的分子相互作用，通过共免疫沉淀的蛋白质重组表达在培养的人胚肾细胞。每一种Dact蛋白都容易与从果蝇到人类的物种的Vangl、Dvl和CK 1 δ/ε蛋白以及PKA和PKC形成复合物。Dact蛋白也与自身和彼此形成复合物;其保守的N-末端亮氨酸拉链结构域，没有已知的结合伴侣，是这种相互作用所必需和足够的，这表明它反映了亮氨酸拉链介导的同源和异源二聚化。我们还发现了较弱的，但保守的，与连环蛋白超家族成员p120 ctn的所有三个Dact旁系同源物的相互作用。与其他先前提出的伙伴（包括大多数其他连环蛋白、GSK 3、LEF/TCF、HDAC 1和TGFβ受体）形成复合物是旁系同源特异性的，相对较弱，和/或对经验条件更敏感。结合已发表的来自靶向敲除小鼠的功能证据，这些数据支持Dact蛋白在涉及Vangl和Dvl的激酶调节生物化学中的保守作用。这有力地表明，所有Dact家族成员的主要作用是在脊椎动物中的PCP途径或分子相关的信号级联中。
The Dact family of scaffold proteins was discovered by virtue of binding to Dvl proteins central to Wnt and Planar Cell Polarity (PCP) signaling. Subsequently Dact proteins have been linked to a growing list of potential partners implicated in β-catenin-dependent and β-catenin-independent forms of Wnt and other signaling. To clarify conserved and non-conserved roles for this protein family, we systematically compared molecular interactions of all three murine Dact paralogs by co-immunoprecipitation of proteins recombinantly expressed in cultured human embryonic kidney cells. Every Dact paralog readily formed complexes with the Vangl, Dvl, and CK1δ/ε proteins of species ranging from fruit flies to humans, as well as with PKA and PKC. Dact proteins also formed complexes with themselves and with each other; their conserved N-terminal leucine-zipper domains, which have no known binding partners, were necessary and sufficient for this interaction, suggesting that it reflects leucine-zipper-mediated homo- and hetero-dimerization. We also found weaker, though conserved, interactions of all three Dact paralogs with the catenin superfamily member p120ctn. Complex formation with other previously proposed partners including most other catenins, GSK3, LEF/TCF, HDAC1, and TGFβ receptors was paralog-specific, comparatively weak, and/or more sensitive to empirical conditions. Combined with published functional evidence from targeted knock-out mice, these data support a conserved role for Dact proteins in kinase-regulated biochemistry involving Vangl and Dvl. This strongly suggests that a principal role for all Dact family members is in the PCP pathway or a molecularly related signaling cascade in vertebrates.
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影响因子：
4.6
作者：
Hikasa, H;Sokol, SY
通讯作者：
Sokol, SY
影响因子：
11.8
作者：
Cheyette, BNR;Waxman, JS;Moon, RT
通讯作者：
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影响因子：
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作者：
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DOI：
10.1523/jneurosci.0354-10.2010
发表时间：
2010-03-24
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Okerlund ND;Kivimäe S;Tong CK;Peng IF;Ullian EM;Cheyette BN
通讯作者：
Cheyette BN
影响因子：
7.7
作者：
Lagathu, Claire;Christodoulides, Constantinos;Virtue, Sam;Cawthorn, William P.;Franzin, Chiara;Kimber, Wendy A.;Nora, Edoardo Dalla;Campbell, Mark;Medina-Gomez, Gema;Cheyette, Benjamin N. R.;Vidal-Puig, Antonio J.;Sethi, Jaswinder K.
通讯作者：
Sethi, Jaswinder K.