IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v6y2015i1d10.1038_ncomms8437.html
   My bibliography  Save this article

Cdk1 phosphorylates the Rac activator Tiam1 to activate centrosomal Pak and promote mitotic spindle formation

Author

Listed:
  • Helen J. Whalley

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

  • Andrew P. Porter

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

  • Zoi Diamantopoulou

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

  • Gavin R. M. White

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

  • Eduardo Castañeda-Saucedo

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

  • Angeliki Malliri

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

Abstract

Centrosome separation is critical for bipolar spindle formation and the accurate segregation of chromosomes during mammalian cell mitosis. Kinesin-5 (Eg5) is a microtubule motor essential for centrosome separation, and Tiam1 and its substrate Rac antagonize Eg5-dependent centrosome separation in early mitosis promoting efficient chromosome congression. Here we identify S1466 of Tiam1 as a novel Cdk1 site whose phosphorylation is required for the mitotic function of Tiam1. We find that this phosphorylation of Tiam1 is required for the activation of group I p21-activated kinases (Paks) on centrosomes in prophase. Further, we show that both Pak1 and Pak2 counteract centrosome separation in a kinase-dependent manner and demonstrate that they act downstream of Tiam1. We also show that depletion of Pak1/2 allows cells to escape monopolar arrest by Eg5 inhibition, highlighting the potential importance of this signalling pathway for the development of Eg5 inhibitors as cancer therapeutics.

Suggested Citation

  • Helen J. Whalley & Andrew P. Porter & Zoi Diamantopoulou & Gavin R. M. White & Eduardo Castañeda-Saucedo & Angeliki Malliri, 2015. "Cdk1 phosphorylates the Rac activator Tiam1 to activate centrosomal Pak and promote mitotic spindle formation," Nature Communications, Nature, vol. 6(1), pages 1-15, November.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms8437
    DOI: 10.1038/ncomms8437
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/ncomms8437
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/ncomms8437?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms8437. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.