Mapping of the molecular determinants involved in the interaction between eps15 and AP-2.

G Iannolo, A E Salcini, I Gaidarov, O B Goodman, J Baulida, G Carpenter, P G Pelicci, P P Di Fiore, J H Keen

    85 Citations (Scopus)

    Abstract

    eps15, a substrate for the epidermal growth factor receptor and other receptor tyrosine kinases, possesses a discrete domain structure with protein-binding properties. It interacts with a number of cellular proteins through an evolutionarily conserved protein-binding domain, the eps15 homology domain, located in its NH2-terminal region. In addition, a proline-rich region, located in the COOH-terminal portion of eps15, can bind to the Src homology 3 domain of the crk proto-oncogene product in vitro. Recently, coimmunoprecipitation between eps15 and AP-2, a major component of coated pits, was reported. Here, we characterize the molecular determinants of the eps15/AP-2 interaction. The AP-2 binding region of eps15 is localized in its COOH-terminal region and spans approximately 80 amino acids. At least three molecular determinants, located at residues 650-660, 680-690, and 720-730, are involved in the binding. AP-2 binds to eps15 through its alpha subunit (alpha-adaptin); in particular, the COOH-terminal region of alpha-adaptin, the so-called alpha-ear, contains the eps15 binding region.
    Original languageEnglish
    JournalCancer Research
    Volume57
    Issue number2
    Pages (from-to)240-5
    Number of pages5
    ISSN0008-5472
    Publication statusPublished - 1997

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