Abi-1 forms an epidermal growth factor-inducible complex with Cbl: role in receptor endocytosis.
The Abl-interactor (Abi) proteins are involved in the regulation of actin polymerization and have recently been shown to modulate epidermal growth factor receptor (EGFR) endocytosis. Here we describe the identification of a novel complex between Abi-1 and the Cbl ubiquitin ligase that is induced by stimulation with EGF. Notably, an ... Abi-1 mutant lacking the SH3 domain (DeltaSH3) fails to interact with Cbl and inhibits EGFR internalization. We show that expression of the Abi-1DeltaSH3 mutant inhibits Cbl accumulation at the plasma membrane after EGF treatment. We have previously shown that the oncogenic Abl tyrosine kinase inhibits EGFR internalization. Here we report that the oncogenic Abl kinase disrupts the EGF-inducible Abi-1/Cbl complex, highlighting the importance of Abl kinases and downstream effectors in the regulation of EGFR internalization. Thus, our work reveals a new role for oncogenic Abl tyrosine kinases in the regulation of the Abi-1/Cbl protein complex and uncovers a role for the Abi-1/Cbl complex in the regulation of EGFR endocytosis.
Mesh Terms:
Animals, COS Cells, Cell Line, Cell Membrane, Cercopithecus aethiops, Cytoskeletal Proteins, Endocytosis, Epidermal Growth Factor, Humans, Mutant Proteins, Protein Binding, Protein Transport, Proto-Oncogene Proteins c-cbl, Receptor, Epidermal Growth Factor, Ubiquitin, src Homology Domains
Animals, COS Cells, Cell Line, Cell Membrane, Cercopithecus aethiops, Cytoskeletal Proteins, Endocytosis, Epidermal Growth Factor, Humans, Mutant Proteins, Protein Binding, Protein Transport, Proto-Oncogene Proteins c-cbl, Receptor, Epidermal Growth Factor, Ubiquitin, src Homology Domains
Cell. Signal.
Date: Jul. 01, 2007
PubMed ID: 17395426
View in: Pubmed Google Scholar
Download Curated Data For This Publication
137792
Switch View:
- Interactions 1