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    Interaction with Shc prevents aberrant Erk activation in the absence of extracellular stimuli

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    nihms582997.pdf
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    Description:
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    Type
    Article
    Authors
    Suen, KinMan
    Lin, Chichuan
    George, Roger R.
    Melo, Fernando A.
    Biggs, Eleanor R.
    Ahmed, Zamal
    Drake, Melanie N.
    Arur, Swathi
    Arold, Stefan T. cc
    Ladbury, John E S D
    KAUST Department
    Biological and Environmental Sciences and Engineering (BESE) Division
    Bioscience Program
    Computational Bioscience Research Center (CBRC)
    Structural Biology and Engineering
    Date
    2013-05-01
    Permanent link to this record
    http://hdl.handle.net/10754/562754
    
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    Abstract
    Control mechanisms that prevent aberrant signaling are necessary to maintain cellular homeostasis. We describe a new mechanism by which the adaptor protein Shc directly binds the MAP kinase Erk, thus preventing its activation in the absence of extracellular stimuli. The Shc-Erk complex restricts Erk nuclear translocation, restraining Erk-dependent transcription of genes, including those responsible for oncogenic growth. The complex forms through unique binding sites on both the Shc PTB domain and the N-terminal lobe of Erk. Upon receptor tyrosine kinase stimulation, a conformational change within Shc - induced through interaction with the phosphorylated receptor - releases Erk, allowing it to fulfill its role in signaling. Thus, in addition to its established role in promoting MAP kinase signaling in stimulated cells, Shc negatively regulates Erk activation in the absence of growth factors and thus could be considered a tumor suppressor in human cells. © 2013 Nature America, Inc. All rights reserved.
    Publisher
    Nature Publishing Group
    Journal
    Nature Structural and Molecular Biology
    DOI
    10.1038/nsmb2557
    10.1038/nsmb.2557
    PubMed ID
    23584453
    ae974a485f413a2113503eed53cd6c53
    10.1038/nsmb2557
    Scopus Count
    Collections
    Articles; Biological and Environmental Science and Engineering (BESE) Division; Bioscience Program; Computational Bioscience Research Center (CBRC)

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