Phosphorylation of the AP2 mu subunit by AAK1 mediates high affinity binding to membrane protein sorting signals.
Phosphorylation of the AP2 mu subunit by AAK1 mediates high affinity binding to membrane protein sorting signals.
复制标题
AAK1对AP2 MU亚基的磷酸化介导了高亲和力与膜蛋白分选信号的结合。
DOI：
10.1083/jcb.200111068
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发表时间：
2002-03-04
影响因子：
7.8
通讯作者：
Honing, Stefan
中科院分区：
文献类型：
--
作者：
Ricotta, Doris;Conner, Sean D;Schmid, Sandra L;von Figura, Kurt;Honing, Stefan
在受体介导的内吞作用中，AP2复合体通过μ2亚基与分选信号结合，并通过β亚基与笼蛋白结合，从而起到连接膜蛋白和网状蛋白的桥梁作用。在这里，我们证明了在体外，AP2与分选信号的结合是通过AP2的μ2亚单位的磷酸化来调节的。与去磷酸化的μ相比，磷酸化的AP2提高了AP2与分选基序的结合亲和力25倍。分选信号的识别不受α或β2亚单位磷酸化状态的影响，这表明μ2的磷酸化是调节AP2与分选信号结合的关键。μ2的磷酸化发生在一个苏氨酸残基(Thr-15 6)上，并由新发现的与AP2相互作用的接头相关激酶AAK1介导。我们认为，在受体介导的内吞作用的初始阶段，通过AAK1对AP2AAK2亚基的磷酸化，确保了AP2与货膜蛋白分选信号的高亲和力结合。
During receptor-mediated endocytosis, AP2 complexes act as a bridge between the cargo membrane proteins and the clathrin coat by binding to sorting signals via the μ2 subunit and to clathrin via the β subunit. Here we show that binding of AP2 to sorting signals in vitro is regulated by phosphorylation of the μ2 subunit of AP2. Phosphorylation of μ2 enhances the binding affinity of AP2 for sorting motifs as much as 25-fold compared with dephosphorylated AP2. The recognition of sorting signals was not affected by the phosphorylation status of the α or β2 subunit, suggesting that phosphorylation of μ2 is critical for regulation of AP2 binding to sorting signals. Phosphorylation of μ2 occurs at a single threonine residue (Thr-156) and is mediated by the newly discovered adaptor-associated kinase, AAK1, which copurifies with AP2. We propose that phosphorylation of the AP2 μ2 subunit by AAK1 ensures high affinity binding of AP2 to sorting signals of cargo membrane proteins during the initial steps of receptor-mediated endocytosis.