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Differential Rac1 signalling by guanine nucleotide exchange factors implicates FLII in regulating Rac1-driven cell migration

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  • Hadir Marei

    (Cell Signalling Group, Cancer Research UK Manchester Institute, The University of Manchester)

  • Alejandro Carpy

    (Proteome Center Tuebingen, Interfaculty Institute for Cell Biology, University of Tuebingen)

  • Anna Woroniuk

    (Cell Signalling Group, Cancer Research UK Manchester Institute, The University of Manchester)

  • Claire Vennin

    (Invasion and Metastasis Group, Garvan Institute of Medical Research, The Kinghorn Cancer Centre, Faculty of Medicine, St Vincent’s Clinical School, University of New South Wales)

  • Gavin White

    (Cell Signalling Group, Cancer Research UK Manchester Institute, The University of Manchester)

  • Paul Timpson

    (Invasion and Metastasis Group, Garvan Institute of Medical Research, The Kinghorn Cancer Centre, Faculty of Medicine, St Vincent’s Clinical School, University of New South Wales)

  • Boris Macek

    (Proteome Center Tuebingen, Interfaculty Institute for Cell Biology, University of Tuebingen)

  • Angeliki Malliri

    (Cell Signalling Group, Cancer Research UK Manchester Institute, The University of Manchester)

Abstract

The small GTPase Rac1 has been implicated in the formation and dissemination of tumours. Upon activation by guanine nucleotide exchange factors (GEFs), Rac1 associates with a variety of proteins in the cell thereby regulating various functions, including cell migration. However, activation of Rac1 can lead to opposing migratory phenotypes raising the possibility of exacerbating tumour progression when targeting Rac1 in a clinical setting. This calls for the identification of factors that influence Rac1-driven cell motility. Here we show that Tiam1 and P-Rex1, two Rac GEFs, promote Rac1 anti- and pro-migratory signalling cascades, respectively, through regulating the Rac1 interactome. In particular, we demonstrate that P-Rex1 stimulates migration through enhancing the interaction between Rac1 and the actin-remodelling protein flightless-1 homologue, to modulate cell contraction in a RhoA-ROCK-independent manner.

Suggested Citation

  • Hadir Marei & Alejandro Carpy & Anna Woroniuk & Claire Vennin & Gavin White & Paul Timpson & Boris Macek & Angeliki Malliri, 2016. "Differential Rac1 signalling by guanine nucleotide exchange factors implicates FLII in regulating Rac1-driven cell migration," Nature Communications, Nature, vol. 7(1), pages 1-16, April.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms10664
    DOI: 10.1038/ncomms10664
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