Arkadia complexes with clathrin adaptor AP2 and regulates EGF signalling
Arkadia complexes with clathrin adaptor AP2 and regulates EGF signalling
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DOI：
10.1093/jb/mvq127
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发表时间：
2010-12-01
影响因子：
2.7
通讯作者：
Miyazono, Kohei
中科院分区：
文献类型：
--
作者：
Mizutani, Anna;Saitoh, Masao;Miyazono, Kohei
Arkadia是转化生长因子（TGF）-β信号传导的正调节剂，其通过其C-末端RING结构域诱导TGF-β信号传导的几种抑制性蛋白的泛素依赖性降解。我们在这里报告，通过酵母双杂交筛选Arkadia结合蛋白，网格蛋白-适配器2（AP 2）复合物的mu 2亚基被确定为Arkadia的相互作用伙伴。在哺乳动物细胞中，Arkadia既存在于细胞核中，也存在于细胞质中。mu 2亚基的C-末端YXX Phi结合结构域与Arkadia的N-末端YALL基序相关。Arkadia在Lys 130处泛素化mu 2亚基。此外，Arkadia与AP 2复合物相互作用，并修饰EGF诱导的表皮生长因子受体（EGFR）的内吞作用。因此，Arkadia似乎通过与AP 2复合物相互作用调节EGFR的内吞作用来调节EGF信号传导。
Arkadia is a positive regulator of transforming growth factor (TGF)-beta signalling that induces ubiquitin-dependent degradation of several inhibitory proteins of TGF-beta signalling through its C-terminal RING domain. We report here that, through yeast-two-hybrid screening for Arkadia-binding proteins, the mu 2 subunit of clathrin-adaptor 2 (AP2) complex was identified as an interacting partner of Arkadia. Arkadia was located in both the nucleus and the cytosol in mammalian cells. The C-terminal YXX Phi-binding domain of the mu 2 subunit associated with the N-terminal YALL motif of Arkadia. Arkadia ubiquitylated the mu 2 subunit at Lys130. In addition, Arkadia interacted with the AP2 complex, and modified endocytosis of epidermal growth factor receptor (EGFR) induced by EGF. Arkadia thus appears to regulate EGF signalling by modulating endocytosis of EGFR through interaction with AP2 complex.