A complex of Shc and Ran-GTPase localises to the cell nucleus

R. George, H. L. Chan, Z. Ahmed, K. M. Suen, C. N. Stevens, J. A. Levitt, K. Suhling, J. Timms, J. E. Ladbury

    Research output: Contribution to journalArticlepeer-review

    10 Scopus citations

    Abstract

    The three isoforms of the adaptor protein Shc play diverse roles in cell signalling. For example, the observation of p46 Shc in the nuclei of hepatocellular carcinoma cells suggests a function quite distinct from the better characterised cytoplasmic role. Ligands responsible for the transport of various Shc isoforms into organelles such as the nucleus have yet to be reported. To identify such ligands a far western approach was used to determine the p52 Shc interactome. The Ran-GTPase nuclear transport protein was identified and found to bind to p52 Shc in vitro with low micromolar affinity. Co-immunoprecipitation, pull down and fluorescence lifetime imaging microscopy experiments in stable cells confirmed cellular interaction and nuclear localisation. The nuclear transport factor protein NTF2, which functions in cohort with Ran, was shown to form a complex with both RAN and Shc, suggesting a mechanism for Shc entry into the nucleus as part of a tertiary complex.

    Original languageEnglish (US)
    Pages (from-to)711-720
    Number of pages10
    JournalCellular and Molecular Life Sciences
    Volume66
    Issue number4
    DOIs
    StatePublished - Feb 2009

    Keywords

    • FLIM
    • Nuclear localisation
    • Nuclear transport
    • Protein complex
    • Proteomics

    ASJC Scopus subject areas

    • Molecular Medicine
    • Molecular Biology
    • Pharmacology
    • Cellular and Molecular Neuroscience
    • Cell Biology

    Fingerprint

    Dive into the research topics of 'A complex of Shc and Ran-GTPase localises to the cell nucleus'. Together they form a unique fingerprint.

    Cite this