PP2A Antagonizes Phosphorylation of Bazooka by PAR-1 to Control Apical-Basal Polarity in Dividing Embryonic Neuroblasts
PP2A Antagonizes Phosphorylation of Bazooka by PAR-1 to Control Apical-Basal Polarity in Dividing Embryonic Neuroblasts
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DOI：
10.1016/j.devcel.2009.04.011
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发表时间：
2009-06-16
影响因子：
11.8
通讯作者：
Wodarz, Andreas
中科院分区：
文献类型：
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作者：
Krahn, Michael P.;Egger-Adam, Diane;Wodarz, Andreas
Bazooka/Par-3 （Baz）是上皮细胞和神经母细胞（NBs）中细胞极性的关键调节因子。PAR-1和aPKC对Baz的磷酸化是其在上皮中的功能所必需的，但对拮抗这些激酶活性的去磷酸化机制或Baz磷酸化与NB极性的相关性知之甚少。我们发现蛋白磷酸酶2A （PP2A）通过其结构A亚基与Baz结合。通过使用磷酸化特异性抗体，我们发现PP2A去磷酸化；Baz位于保守的丝氨酸残基1085上，从而拮抗PAR-1的激酶活性。PP2A功能的丧失导致NBs的极性完全逆转，从而产生“颠倒”极性表型。PAR-1或Baz的过表达，或14-3-3蛋白结合磷酸化Baz的突变，导致本质上相同的表型，表明PAR-1和PP2A对Baz磷酸化作用的平衡决定了NIB的极性。
Bazooka/Par-3 (Baz) is a key regulator of cell polarity in epithelial cells and neuroblasts (NBs). Phosphorylation of Baz by PAR-1 and aPKC is required for its function in epithelia, but little is known about the dephosphorylation mechanisms that antagonize the activities of these kinases or about the relevance of Baz phosphorylation for NB polarity. We found that protein phosphatase 2A (PP2A) binds to Baz via its structural A subunit. By using phospho-specific antibodies, we show that PP2A dephosphorylates; Baz at the conserved serine residue 1085 and thereby antagonizes the kinase activity of PAR-1. Loss of PP2A function leads to complete reversal of polarity in NBs, giving rise to an "upside-down" polarity phenotype. Overexpression of PAR-1 or Baz, or mutation of 14-3-3 proteins that bind phosphorylated Baz, causes essentially the same phenotype, indicating that the balance of PAR-1 and PP2A effects on Baz phosphorylation determines NIB polarity.