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In vivo and in vitro Studies of Adaptor-clathrin Interaction
Published on: January 26, 2011
Arkadia complexes with clathrin adaptor AP2 and regulates EGF signalling
Anna Mizutani1, Masao Saitoh, Takeshi Imamura
1Department of Molecular Pathology, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, Japan.
Journal of Biochemistry
|October 23, 2010
Summary
Arkadia protein regulates transforming growth factor-beta (TGF-β) and epidermal growth factor (EGF) signaling. It interacts with the AP2 complex, affecting EGF receptor endocytosis and TGF-β pathway modulation.
Area of Science:
- Cell Biology
- Molecular Biology
- Signal Transduction
Background:
- Arkadia is a positive regulator of transforming growth factor (TGF)-β signaling.
- It functions by ubiquitin-dependent degradation of inhibitory proteins via its C-terminal RING domain.
Purpose of the Study:
- To identify Arkadia-binding proteins.
- To investigate the interaction between Arkadia and the AP2 complex.
- To elucidate Arkadia's role in epidermal growth factor receptor (EGFR) endocytosis and signaling.
Main Methods:
- Yeast-two-hybrid screening to identify Arkadia-interacting proteins.
- Cellular localization studies in mammalian cells.
- Analysis of protein ubiquitylation and complex interactions.
- Investigation of epidermal growth factor (EGF) signaling and EGFR endocytosis.
Main Results:
- The µ2 subunit of the clathrin-adaptor 2 (AP2) complex was identified as an Arkadia-binding protein.
- Arkadia interacts with the AP2 complex and ubiquitylates the µ2 subunit.
- Arkadia's YALL motif binds to the µ2 subunit's YXXΦ-binding domain.
- Arkadia modulates EGF-induced endocytosis of EGFR through its interaction with AP2.
Conclusions:
- Arkadia interacts with the AP2 complex, influencing EGFR endocytosis and EGF signaling.
- This interaction suggests a novel mechanism for Arkadia in regulating cellular signaling pathways beyond TGF-β.
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