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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Protein phosphatase 1 regulates the phosphorylation state of the polarity scaffold Par-3
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Protein phosphatase 1 regulates the phosphorylation state of the polarity scaffold Par-3

机译：蛋白磷酸酶1调节极性支架Par-3的磷酸化状态

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摘要

Phosphorylation of the polarity protein Par-3 by the serine/ threonine kinases aPKCζ/ι and Par-1 (EMK1/MARK2) regulates various aspects of epithelial cell polarity, but little is known about the mechanisms by which these posttranslational modifications are reversed. We find that the serine/threonine protein phosphatase PP1 (predominantly the α isoform) binds Par-3, which localizes to tight junctions in MDCKII cells. PP1α can associate with multiple sites on Par-3 while retaining its phosphatase activity. By using a quantitative mass spectrometry-based technique, multiple reaction monitoring, we show that PP1 α specifically dephosphorylates Ser-144 and Ser-824 of mouse Par-3, as well as a peptide encompassing Ser-885. Consistent with these observations, PP1α regulates the binding of 14-3-3 proteins and the atypical protein kinase C (aPKC) ζ to Par-3. Furthermore, the induced expression of a catalytically inactive mutant of PP1 α severely delays the formation of functional tight junctions in MDCKII cells. Collectively, these results show that Par-3 functions as a scaffold, coordinating both serine/threonine kinases and the PP1α phosphatase, thereby providing dynamic control of the phosphorylation events that regulate the Par-3/aPKC complex.
机译：丝氨酸/苏氨酸激酶aPKCζ/ a和Par-1（EMK1 / MARK2）对极性蛋白Par-3的磷酸化调节了上皮细胞极性的各个方面，但是对于这些翻译后修饰被逆转的机制知之甚少。我们发现，丝氨酸/苏氨酸蛋白磷酸酶PP1（主要是α亚型）结合了Par-3，后者定位于MDCKII细胞中的紧密连接。 PP1α可以与Par-3上的多个位点缔合，同时保留其磷酸酶活性。通过使用基于定量质谱的技术，进行多反应监测，我们发现PP1α特异性地使小鼠Par-3的Ser-144和Ser-824以及包含Ser-885的肽脱磷酸。与这些观察结果一致，PP1α调节14-3-3蛋白和非典型蛋白激酶C（aPKC）ζ与Par-3的结合。此外，PP1α催化失活突变体的诱导表达严重延迟了MDCKII细胞中功能性紧密连接的形成。总的来说，这些结果表明，Par-3充当支架，协调丝氨酸/苏氨酸激酶和PP1α磷酸酶，从而动态调节调节Par-3 / aPKC复合物的磷酸化事件。

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