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.
Rotem-Yehudar
R
R
Department of Cell Research and Immunology, Tel-Aviv University, Ramat-Aviv, 69978, Tel-Aviv, Israel.
Galperin
E
E
Horowitz
M
M
D016475:3T3 Cells; D033942:Adaptor Proteins, Vesicular Transport; D000818:Animals; D001665:Binding Sites; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002966:Clathrin / Q000378:metabolism; D016228:Endothelial Growth Factors / Q000235:genetics*; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D008222:Lymphokines / Q000235:genetics*; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D050766:Qb-SNARE Proteins; D050767:Qc-SNARE Proteins; D051381:Rats; D017526:Receptor, IGF Type 1 / Q000737:chemistry / Q000378:metabolism*; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013574:Synaptosomes / Q000378:metabolism; D014162:Transfection; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D033921:Vesicular Transport Proteins
D033942:Adaptor Proteins, Vesicular Transport; D002352:Carrier Proteins; D002966:Clathrin; C485640:Ehd1 protein, mouse; D016228:Endothelial Growth Factors; D008222:Lymphokines; D008565:Membrane Proteins; D050766:Qb-SNARE Proteins; D050767:Qc-SNARE Proteins; D011994:Recombinant Proteins; C486621:Snap29 protein, mouse; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D033921:Vesicular Transport Proteins; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1