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.
Tanos
Barbara E
BE
Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC 27710, USA.
Pendergast
Ann Marie
AM
D000818:Animals; D019556:COS Cells; D002460:Cell Line; D002462:Cell Membrane / Q000187:drug effects; D002522:Chlorocebus aethiops; D003598:Cytoskeletal Proteins / Q000737:chemistry / Q000378:metabolism*; D004705:Endocytosis / Q000187:drug effects*; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D066246:ErbB Receptors / Q000378:metabolism*; D006801:Humans; D050505:Mutant Proteins / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects; D021381:Protein Transport / Q000187:drug effects; D050721:Proto-Oncogene Proteins c-cbl / Q000737:chemistry / Q000378:metabolism*; D025801:Ubiquitin / Q000378:metabolism; D018909:src Homology Domains
D003598:Cytoskeletal Proteins; D050505:Mutant Proteins; D025801:Ubiquitin; D004815:Epidermal Growth Factor; D050721:Proto-Oncogene Proteins c-cbl; D066246:ErbB Receptors