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    GEFs: Dual regulation of Rac1 signaling.

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    Authors
    Marei, Hadir
    Malliri, Angeliki
    Affiliation
    Cell Signaling Group, Cancer Research UK Manchester Institute, The University of Manchester , Manchester M20 4BX
    Issue Date
    2016
    
    Metadata
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    Abstract
    GEFs play a critical role in regulating Rac1 signaling. They serve as signaling nodes converting upstream signals into downstream Rac1-driven cellular responses. Through associating with membrane-bound Rac1, GEFs facilitate the exchange of GDP for GTP, thereby activating Rac1. As a result, Rac1 undergoes conformational changes that mediate its interaction with downstream effectors, linking Rac1 to a multitude of physiological and pathological processes. Interestingly, at least 20 GEFs have been shown to activate Rac1, suggesting a more complex role of GEFs in regulating Rac1 signaling apart from promoting the exchange of GDP for GTP. Indeed, accumulating evidence implicates GEFs in directing the specificity of Rac1-driven signaling cascades, although the underlying mechanisms were poorly defined. Recently, through conducting a comparative study, we highlighted the role of two Rac-specific GEFs, Tiam1 and P-Rex1, in dictating the biological outcome downstream of Rac1. Importantly, further proteomic analysis uncovered a GEF activity-independent role of both GEFs in modulating the Rac1 interactome, which results in the stimulation of GEF-specific signaling cascades. Here, we provide an overview of our recent findings and discuss the role of GEFs as master regulators of Rac1 signaling with a particular focus on GEF-mediated modulation of cell migration following Rac1 activation.
    Citation
    GEFs: Dual regulation of Rac1 signaling. 2016:0 Small GTPases
    Journal
    Small GTPases
    URI
    http://hdl.handle.net/10541/617030
    DOI
    10.1080/21541248.2016.1202635
    PubMed ID
    27314616
    Type
    Meetings and Proceedings
    Language
    en
    ISSN
    2154-1256
    ae974a485f413a2113503eed53cd6c53
    10.1080/21541248.2016.1202635
    Scopus Count
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    All Paterson Institute for Cancer Research

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