Association of insulin-like growth factor 1 receptor with EHD1 and SNAP29.

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.
Mesh Terms:
3T3 Cells, Adaptor Proteins, Vesicular Transport, Animals, Binding Sites, Carrier Proteins, Clathrin, Endothelial Growth Factors, Insulin-Like Growth Factor I, Lymphokines, Membrane Proteins, Mice, Promoter Regions, Genetic, Protein Binding, Qb-SNARE Proteins, Qc-SNARE Proteins, Rats, Receptor, IGF Type 1, Recombinant Proteins, Signal Transduction, Synaptosomes, Transfection, Vascular Endothelial Growth Factor A, Vascular Endothelial Growth Factors, Vesicular Transport Proteins
J. Biol. Chem.
Date: Aug. 31, 2001
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