Ricotta Doris, Conner Sean D, Schmid Sandra L, von Figura Kurt, Honing Stefan
Institute for Biochemistry II, University of Göttingen, 37073 Göttingen, Germany.
J Cell Biol. 2002 Mar 4;156(5):791-5. doi: 10.1083/jcb.200111068.
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 mu 2 subunit and to clathrin via the beta subunit. Here we show that binding of AP2 to sorting signals in vitro is regulated by phosphorylation of the mu 2 subunit of AP2. Phosphorylation of mu 2 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 alpha or beta 2 subunit, suggesting that phosphorylation of mu 2 is critical for regulation of AP2 binding to sorting signals. Phosphorylation of mu 2 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 mu 2 subunit by AAK1 ensures high affinity binding of AP2 to sorting signals of cargo membrane proteins during the initial steps of receptor-mediated endocytosis.
在受体介导的内吞作用过程中，AP2复合物通过μ2亚基与分选信号结合，并通过β亚基与网格蛋白结合，从而在货物膜蛋白与网格蛋白包被之间充当桥梁。在此我们表明，体外AP2与分选信号的结合受AP2的μ2亚基磷酸化的调控。与去磷酸化的AP2相比，μ2的磷酸化使AP2对分选基序的结合亲和力提高了多达25倍。分选信号的识别不受α或β2亚基磷酸化状态的影响，这表明μ2的磷酸化对于调控AP2与分选信号的结合至关重要。μ2的磷酸化发生在单个苏氨酸残基（Thr-156）上，由新发现的衔接蛋白相关激酶AAK1介导，AAK1与AP2共同纯化。我们提出，在受体介导的内吞作用的初始步骤中，AAK1对AP2 μ2亚基的磷酸化确保了AP2与货物膜蛋白分选信号的高亲和力结合。
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