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 α-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.
Original language | English |
---|---|
Pages (from-to) | 33054-33060 |
Number of pages | 7 |
Journal | Journal of Biological Chemistry |
Volume | 276 |
Issue number | 35 |
DOIs | |
State | Published - Aug 31 2001 |
ASJC Scopus subject areas
- Biochemistry
- Molecular Biology
- Cell Biology