Modulation of fat:dachsous binding by the cadherin domain kinase four-jointed.
Modulation of fat:dachsous binding by the cadherin domain kinase four-jointed.
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DOI：
10.1016/j.cub.2010.04.016
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发表时间：
2010-05-11
期刊：
影响因子：
9.2
通讯作者：
Irvine, Kenneth D.
中科院分区：
文献类型：
--
作者：
Simon, Michael A.;Xu, Aiguo;Ishikawa, Hiroyuki O.;Irvine, Kenneth D.
除了形态发生素信号传导中的定量差异指定不同的细胞命运之外，形态发生素梯度的矢量和斜率可以影响平面细胞极性（PCP）和生长。非典型钙粘蛋白脂肪在这一过程中起着核心作用。脂肪通过不同的下游途径调节PCP和生长，这两种途径似乎都涉及细胞内分子极性的建立[综述见]。脂肪活性受非典型钙粘蛋白Dachsous（Ds）和蛋白激酶Four-jointed（Fj）调节，它们在许多组织中以相反的梯度表达。对它们对Fat影响的研究表明，Fat受Fj和Ds表达梯度的载体和斜率的调节，但这是如何实现的仍然未知。在这里，我们确定和表征的分子机制，细胞解释Fj表达梯度，以抑制脂肪活性。我们证明Fj既促进Fat与其配体Ds结合的能力，又抑制Ds与Fat结合的能力。作为这些相反的Fj活性的结果，Fj表达水平不同的细胞的并置导致不对称的Fat-Ds结合。我们还表明，Fj对脂肪的影响是脂肪磷酸化的直接后果，并确定一个重要的Fj刺激Fat-Ds结合的磷酸化位点。我们的研究结果定义了一种分子机制，通过这种机制，形态发生梯度可以驱动脂肪活性的极化，从而影响PCP和发育中组织的生长。
In addition to quantitative differences in morphogen signaling specifying distinct cell fates, the vector and slope of morphogen gradients can influence planar cell polarity (PCP) and growth. The atypical cadherin Fat plays a central role in this process. Fat regulates PCP and growth through distinct downstream pathways, both of which appear to involve the establishment of molecular polarity within cells [reviewed in ]. Fat activity is regulated by the atypical cadherin Dachsous (Ds), and the protein kinase Four-jointed (Fj), which are expressed in opposing gradients in many tissues. Studies of their influence on Fat have implied that Fat is regulated by the vector and slope of the Fj and Ds expression gradients but how this is achieved remained unknown. Here, we identify and characterize the molecular mechanism by which cells interpret a Fj expression gradient to polarize Fat activity. We demonstrate that Fj both promotes the ability of Fat to bind to its ligand Ds, and inhibits the ability of Ds to bind Fat. As a result these opposing Fj activities, the juxtaposition of cells differing in their levels of Fj expression results in asymmetric Fat-Ds binding. We also show that the influence of Fj on Fat is a direct consequence of Fat phosphorylation, and identify a phosphorylation site important for the stimulation of Fat-Ds binding by Fj. Our results define a molecular mechanism by which a morphogen gradient can drive the polarization of Fat activity to influence PCP and growth in developing tissues.
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四关节是一种高尔基激酶，可磷酸化钙粘蛋白结构域的子集。
影响因子：
56.9
作者：
Ishikawa, Hiroyuki O.;Takeuchi, Hideyuki;Haltiwanger, Robert S.;Irvine, Kenneth D.
通讯作者：
Irvine, Kenneth D.
影响因子：
4.6
作者：
Strutt, H;Mundy, J;Strutt, D
通讯作者：
Strutt, D
影响因子：
9.2
作者：
Casal, J;Struhl, G;Lawrence, PA
通讯作者：
Lawrence, PA
影响因子：
9.2
作者：
Sopko, Richelle;Silva, Elizabeth;McNeill, Helen
通讯作者：
McNeill, Helen
DOI：
10.1073/pnas.0805201105
发表时间：
2008-09-30
影响因子：
11.1
作者：
Willecke, Maria;Hamaratoglu, Fisun;Halder, Georg
通讯作者：
Halder, Georg