Abstract
Ligand-induced receptor-mediated endocytosis plays a central role in regulating signaling conveyed by tyrosine kinase receptors. This process depends on the recruitment of the adaptor protein 2 (AP-2) complex, clathrin, dynamin, and other accessory proteins to the ligand-bound receptor. We show here that besides AP-2 and clathrin, two other proteins participate in the endocytic process of the insulin-like growth factor receptor (IGF-1R); they are EHD1, an Eps15 homology (EH) domain-containing protein 1, and SNAP29, a synaptosomal-associated protein. EHD1 and SNAP29 form complexes with alpha-adaptin of AP-2 and co-localize in endocytic vesicles, indicating a role for them in endocytosis. EHD1 and SNAP29 interact directly with each other and are present in complexes with IGF-1R. After IGF-1 induction, EHD1 and IGF-1R co-localize intracellularly. Overexpression of EHD1 in Chinese hamster ovary cells represses IGF-1-mediated signaling, as measured by mitogen-activated protein kinase phosphorylation and Akt phosphorylation, indicating that EHD1 plays a role as a down-regulator in IGF-1 signaling pathway.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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3T3 Cells
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Adaptor Proteins, Vesicular Transport
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Animals
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Binding Sites
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Carrier Proteins / chemistry
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Carrier Proteins / genetics
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Carrier Proteins / metabolism*
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Clathrin / metabolism
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Endothelial Growth Factors / genetics*
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Insulin-Like Growth Factor I / pharmacology
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Lymphokines / genetics*
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Membrane Proteins / metabolism
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Mice
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Promoter Regions, Genetic
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Protein Binding
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Qb-SNARE Proteins
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Qc-SNARE Proteins
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Rats
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Receptor, IGF Type 1 / chemistry
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Receptor, IGF Type 1 / metabolism*
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Recombinant Proteins / chemistry
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Recombinant Proteins / metabolism
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Signal Transduction / drug effects
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Signal Transduction / physiology
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Synaptosomes / metabolism
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Transfection
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Vascular Endothelial Growth Factor A
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Vascular Endothelial Growth Factors
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Vesicular Transport Proteins*
Substances
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Adaptor Proteins, Vesicular Transport
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Carrier Proteins
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Clathrin
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Ehd1 protein, mouse
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Endothelial Growth Factors
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Lymphokines
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Membrane Proteins
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Qb-SNARE Proteins
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Qc-SNARE Proteins
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Recombinant Proteins
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Snap29 protein, mouse
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Vascular Endothelial Growth Factor A
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Vascular Endothelial Growth Factors
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Vesicular Transport Proteins
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Insulin-Like Growth Factor I
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Receptor, IGF Type 1