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          Institute: MPI für molekulare Physiologie     Collection: Abteilung II - Systemische Zellbiologie     Display Documents



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ID: 427499.0, MPI für molekulare Physiologie / Abteilung II - Systemische Zellbiologie
c-Cbl/Sli-1 regulates endocytic sorting and ubiquitination of the epidermal growth factor receptor
Authors:Levkowitz, G.; Waterman, H.; Zamir, E.; Kam, Z.; Oved, S.; Langdon, W. Y.; Beguinot, L.; Geiger, B.; Yarden, Y.
Date of Publication (YYYY-MM-DD):1998-12-01
Title of Journal:Genes & Development
Journal Abbrev.:Genes Dev
Volume:12
Issue / Number:23
Start Page:3663
End Page:3674
Review Status:not specified
Audience:Not Specified
Abstract / Description:Ligand-induced down-regulation of two growth factor receptors, EGF receptor (ErbB-1) and ErbB-3, correlates with differential ability to recruit c-Cbl, whose invertebrate orthologs are negative regulators of ErbB. We report that ligand-induced degradation of internalized ErbB-1, but not ErbB-3, is mediated by transient mobilization of a minor fraction of c-Cbl into ErbB-1-containing endosomes. This recruitment depends on the receptor's tyrosine kinase activity and an intact carboxy-terminal region. The alternative fate is recycling of internalized ErbBs to the cell surface. Cbl-mediated receptor sorting involves covalent attachment of ubiquitin molecules, and subsequent lysosomal and proteasomal degradation. The oncogenic viral form of Cbl inhibits down-regulation by shunting endocytosed receptors to the recycling pathway. These results reveal an endosomal sorting machinery capable of controlling the fate, and, hence, signaling potency, of growth factor receptors.
Free Keywords:Biological Transport; Cell Compartmentation; Down-Regulation; *Endocytosis; Endosomes; Ligands; Models, Biological; Mutation; Oncogene Protein v-cbl; Protein Processing, Post-Translational; Protein-Tyrosine Kinases/metabolism; Proto-Oncogene Proteins/genetics/*metabolism; Proto-Oncogene Proteins c-cbl; Receptor, Epidermal Growth Factor/genetics/*metabolism; Receptor, erbB-3; Retroviridae Proteins, Oncogenic/*metabolism; Signal Transduction; *Ubiquitin-Protein Ligases; Ubiquitins/*metabolism
External Publication Status:published
Document Type:Article
Communicated by:Jürgen Block
Affiliations:MPI für molekulare Physiologie/Abteilung II - Systemische Zellbiologie/AG Dr. E. Zamir
External Affiliations:%G eng
Identifiers:ISSN:0890-9369 (Print) [ID No:1]
URL:http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=... [ID No:2]
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