Abstract:
:Cdc42-associated tyrosine kinase 1 (ACK1) is a specific down-stream effector of Cdc42, a Rho family small G-protein. Previous studies have shown that ACK1 interacts with clathrin heavy chain and is involved in clathrin-coated vesicle endocytosis. Here we report that ACK1 interacted with epidermal growth factor receptor (EGFR) upon EGF stimulation via a region at carboxy terminus that is highly homologous to Gene-33/Mig-6/RALT. The interaction of ACK1 with EGFR was dependent on the kinase activity or tyrosine phosphorylation of EGFR. Immunofluorescent staining using anti-EGFR and GFP-ACK1 indicates that ACK1 was colocalized with EGFR on EEA-1 positive vesicles upon EGF stimulation. Suppression of the expression of ACK1 by ACK-RNAi inhibited ligand-induced degradation of EGFR upon EGF stimulation, suggesting that ACK1 plays an important role in regulation of EGFR degradation in cells. Furthermore, we identified ACK1 as an ubiquitin-binding protein. Through an ubiquitin-association (Uba) domain at the carboxy terminus, ACK1 binds to both poly- and mono-ubiquitin. Overexpression of the Uba domain-deletion mutant of ACK1 blocked the ligand-dependent degradation of EGFR, suggesting that ACK1 regulates EGFR degradation via its Uba domain. Taken together, our studies suggest that ACK1 senses signal of EGF and regulates ligand-induced degradation of EGFR.
journal_name
Mol Biol Celljournal_title
Molecular biology of the cellauthors
Shen F,Lin Q,Gu Y,Childress C,Yang Wdoi
10.1091/mbc.e06-02-0142subject
Has Abstractpub_date
2007-03-01 00:00:00pages
732-42issue
3eissn
1059-1524issn
1939-4586pii
E06-02-0142journal_volume
18pub_type
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journal_title:Molecular biology of the cell
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更新日期:1994-12-01 00:00:00
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pub_type: 杂志文章
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journal_title:Molecular biology of the cell
pub_type: 杂志文章
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pub_type: 杂志文章,评审
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journal_title:Molecular biology of the cell
pub_type: 杂志文章
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journal_title:Molecular biology of the cell
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journal_title:Molecular biology of the cell
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journal_title:Molecular biology of the cell
pub_type: 杂志文章
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更新日期:2005-04-01 00:00:00
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