Identification of preferred protein interactions by phage-display of the human Src homology-3 proteome

Satu Kärkkäinen, Marita Hiipakka, Jing-Huan Wang, Iivari Kleino, Marika Vähä-Jaakkola, G. Herman Renkema, Michael Liss, Ralf Wagner, Kalle Saksela

    Tutkimustuotos: ArtikkelijulkaisuArtikkeliTieteellinenvertaisarvioitu

    Abstrakti

    We have determined the human genome to contain 296 different Src homology-3 (SH3) domains and cloned them into a phage-display vector. This provided a powerful and unbiased system for simultaneous assaying of the complete human SH3 proteome for the strongest binding to target proteins of interest, without the limitations posed by short linear peptide ligands or confounding variables of more indirect methods for protein interaction screening. Studies involving three ligand proteins, human immunodeficiency virus-1 Nef, p21-activated kinase (PAK) 2 and ADAM15, showed previously reported as well as novel SH3 partners with nanomolar affinities specific for them. This argues that SH3 domains may have a more dominant role in directing cellular protein interactions than has been assumed. Besides showing potentially important new SH3-directed interactions, these studies also led to the discovery of novel signalling proteins, such as the PAK2-binding adaptor protein POSH2 and the ADAM15-binding sorting nexin family member SNX30.
    Alkuperäiskielienglanti
    LehtiEMBO Reports
    Vuosikerta7
    Numero2
    Sivut186-191
    Sivumäärä6
    ISSN1469-221X
    DOI - pysyväislinkit
    TilaJulkaistu - 2006
    OKM-julkaisutyyppiA1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä, vertaisarvioitu

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