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

Department of Cell Research and Immunology, Tel-Aviv University, Ramat-Aviv, 69978, Tel-Aviv, Israel.
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. Aug. 31, 2001; 276(35);33054-60 [PUBMED:11423532]
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