Curtin University Homepage
  • Library
  • Help
    • Admin

    espace - Curtin’s institutional repository

    JavaScript is disabled for your browser. Some features of this site may not work without it.
    View Item 
    • espace Home
    • espace
    • Curtin Research Publications
    • View Item
    • espace Home
    • espace
    • Curtin Research Publications
    • View Item

    Role of Focal Adhesion Tyrosine Kinases in GPVI-Dependent Platelet Activation and Reactive Oxygen Species Formation

    Access Status
    Open access via publisher
    Authors
    Carrim, N.
    Walsh, T.
    Consonni, A.
    Torti, M.
    Berndt, Michael
    Metharom, Pat
    Date
    2014
    Type
    Journal Article
    
    Metadata
    Show full item record
    Citation
    Carrim, N. and Walsh, T. and Consonni, A. and Torti, M. and Berndt, M. and Metharom, P. 2014. Role of Focal Adhesion Tyrosine Kinases in GPVI-Dependent Platelet Activation and Reactive Oxygen Species Formation. PloS One. 9 (11).
    Source Title
    PloS One
    DOI
    10.1371/journal.pone.0113679
    ISSN
    1932-6203
    Faculty
    Faculty of Health Sciences
    URI
    http://hdl.handle.net/20.500.11937/29835
    Collection
    • Curtin Research Publications
    Abstract

    BackgroundWe have previously shown the presence of a TRAF4/p47phox/Hic5/Pyk2 complex associated with the platelet collagen receptor, GPVI, consistent with a potential role of this complex in GPVI-dependent ROS formation. In other cell systems, NOX-dependent ROS formation is facilitated by Pyk2, which along with its closely related homologue FAK are known to be activated and phosphorylated downstream of ligand binding to GPVI.AimsTo evaluate the relative roles of Pyk2 and FAK in GPVI-dependent ROS formation and to determine their location within the GPVI signaling pathway.Methods and ResultsHuman and mouse washed platelets (from WT or Pyk2 KO mice) were pre-treated with pharmacological inhibitors targeting FAK or Pyk2 (PF-228 and Tyrphostin A9, respectively) and stimulated with the GPVI-specific agonist, CRP. FAK, but not Pyk2, was found to be essential for GPVI-dependent ROS production and aggregation. Subsequent human platelet studies with PF-228 confirmed FAK is essential for GPVI-mediated phosphatidylserine exposure, a-granule secretion (P-selectin (CD62P) surface expression) and integrin aIIbß3 activation. To determine the precise location of FAK within the GPVI pathway, we analyzed the effect of PF-228 inhibition in CRP-stimulated platelets in conjunction with immunoprecipitation and pulldown analysis to show that FAK is downstream of Lyn, Spleen tyrosine kinase (Syk), PI3-K and Bruton's tyrosine kinase (Btk) and upstream of Rac1, PLC?2, Ca2+ release, PKC, Hic-5, NOX1 and aIIbß3 activation.ConclusionOverall, these data suggest a novel role for FAK in GPVI-dependent ROS formation and platelet activation and elucidate a proximal signaling role for FAK within the GPVI pathway.

    Related items

    Showing items related by title, author, creator and subject.

    • The role of Nox1 and Nox2 in GPVI-dependent platelet activation and thrombus formation
      Walsh, T.; Berndt, Michael; Carrim, N.; Cowman, J.; Kenny, D.; Metharom, Pat (2014)
      Background: Activation of the platelet-specific collagen receptor, glycoprotein (GP) VI, induces intracellular reactive oxygen species (ROS) production; however the relevance of ROS to GPVI-mediated platelet responses ...
    • Oligomeric and fibrillar amyloid beta 42 induce platelet aggregation partially through GPVI
      Elaskalani, O.; Khan, I.; Morici, M.; Matthysen, C.; Sabale, M.; Martins, R.; Verdile, G.; Metharom, Pat (2017)
      © 2017 Taylor & Francis The effects of the Alzheimer’s disease (AD)-associated Amyloid-ß (Aß) peptides on platelet aggregation have been previously assessed, but most of these studies focused on Aß40 species. It also ...
    • Thrombin-induced reactive oxygen species generation in platelets: A novel role for protease-activated receptor 4 and GPIba.
      Carrim, N.; Arthur, J.; Hamilton, J.; Gardiner, E.; Andrews, R.; Moran, N.; Berndt, Michael; Metharom, Pat (2015)
      BACKGROUND: Platelets are essential for maintaining haemostasis and play a key role in the pathogenesis of cardiovascular disease. Upon ligation of platelet receptors through subendothelial matrix proteins, intracellular ...
    Advanced search

    Browse

    Communities & CollectionsIssue DateAuthorTitleSubjectDocument TypeThis CollectionIssue DateAuthorTitleSubjectDocument Type

    My Account

    Admin

    Statistics

    Most Popular ItemsStatistics by CountryMost Popular Authors

    Follow Curtin

    • 
    • 
    • 
    • 
    • 

    CRICOS Provider Code: 00301JABN: 99 143 842 569TEQSA: PRV12158

    Copyright | Disclaimer | Privacy statement | Accessibility

    Curtin would like to pay respect to the Aboriginal and Torres Strait Islander members of our community by acknowledging the traditional owners of the land on which the Perth campus is located, the Whadjuk people of the Nyungar Nation; and on our Kalgoorlie campus, the Wongutha people of the North-Eastern Goldfields.