4.2 Article

Arkadia complexes with clathrin adaptor AP2 and regulates EGF signalling

期刊

JOURNAL OF BIOCHEMISTRY
卷 148, 期 6, 页码 733-741

出版社

OXFORD UNIV PRESS
DOI: 10.1093/jb/mvq127

关键词

AP2; Arkadia; endocytosis; TGF-beta; ubiquitylation

资金

  1. Ministry of Education, Culture, Sports, Science and Technology of Japan
  2. Japan Society for the Promotion of Science
  3. Ishidsu Shun Memorial Scholarship

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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.

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