Phosphorylation-dependent binding of 14-3-3 to the polarity protein Par3 regulates cell polarity in mammalian epithelia
Phosphorylation-dependent binding of 14-3-3 to the polarity protein Par3 regulates cell polarity in mammalian epithelia
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DOI：
10.1016/j.cub.2003.11.020
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发表时间：
2003-12-02
期刊：
影响因子：
9.2
通讯作者：
Margolis, B
中科院分区：
文献类型：
--
作者：
Hurd, TW;Fan, SL;Margolis, B
C.已证明线虫的分配缺陷（Par）蛋白对于细胞极性的建立是必需的。在哺乳动物上皮中，Par 3/Par 6/aPKC极性复合物定位于紧密连接，并调节其相对于基底外侧和顶端膜结构域的形成和定位。在这里，我们证明了一个以前未描述的磷酸化依赖的相互作用之间的哺乳动物同源的C。线虫极性蛋白Par 5，14-3-3，和紧密连接相关蛋白Par 3。我们确定磷酸化的丝氨酸144作为14-3-3结合位点。含有丝氨酸144突变为丙氨酸（S144 A）的Par 3突变体的表达导致上皮细胞极性的缺陷。此外，14-3-3的过表达导致极性的严重破坏，而14-3-3突变体的过表达在与磷蛋白的结合中有缺陷，对细胞极性没有影响。总之，这些数据表明一种新的磷酸化依赖性机制，通过14-3-3结合调节Par 3/Par 6/aPKC极性复合物的功能。
The mammalian homologs of the C. elegans partitioning-defective (Par) proteins have been demonstrated to be necessary for establishment of cell polarity. In mammalian epithelia, the Par3/Par6/aPKC polarity complex is localized to the tight junction and regulates its formation and positioning with respect to basolateral and apical membrane domains. Here we demonstrate a previously undescribed phosphorylation-dependent interaction between a mammalian homolog of the C. elegans polarity protein Par5, 14-3-3, and the tight junction-associated protein Par3. We identify phosphorylated serine 144 as a site of 14-3-3 binding. Expression of a Par3 mutant that contains serine 144 mutated to alanine (S144A) results in defects in epithelial cell polarity. In addition, overexpression of 14-3-3 results in a severe disruption of polarity, whereas overexpression of a 14-3-3 mutant that is defective in binding to phosphoproteins has no effect on cell polarity. Together, these data suggest a novel, phosphorylation-dependent mechanism that regulates the function of the Par3/Par6/aPKC polarity complex through 14-3-3 binding.