Journal
FASEB JOURNAL
Volume 21, Issue 11, Pages 2849-2862Publisher
FEDERATION AMER SOC EXP BIOL
DOI: 10.1096/fj.06-7925com
Keywords
negative regulators; ubiquitin ligase; nuclear translocation
Categories
Ask authors/readers for more resources
The ErbB- 4 receptors are unique in the EGFR/ ErbB family for the ability to associate with WW domain- containing proteins. To identify new ligands of the cytoplasmic tail of ErbB- 4, we panned a brain cDNA phage library with ErbB- 4 peptides containing sequence motifs corresponding to putative docking sites for class- I WW domains. This approach led to identification of AIP4/ Itch, a member of the Nedd4- like family of E3 ubiquitin protein ligases, as a protein that specifically interacts with and ubiquitinates ErbB- 4 in vivo. Interaction with the ErbB- 4 receptors occurs via the WW domains of AIP4/ Itch. Functional analyses demonstrate that AIP4/ Itch is recruited to the ErbB- 4 receptor to promote its polyubiquitination and degradation, thereby regulating stability of the receptor and access of receptor intracellular domains to the nuclear compartment. These findings expand our understanding of the mechanisms contributing to the integrity of the ErbB signaling network and mechanistically link the cellular ubiquitination pathway of AIP4/ Itch to the ErbB- 4 receptor.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available