WNT-3a modulates platelet function by regulating small GTPase activity

Brian M Steele, Matthew T Harper, Albert P Smolenski, Naheda Alkazemi, Alastair W Poole, Desmond J Fitzgerald, Patricia B Maguire

Research output: Contribution to journalArticle (Academic Journal)

10 Citations (Scopus)

Abstract

Here we provide evidence that WNT-3a modulates platelet function by regulating the activity of four key GTPase proteins: Rap1, Cdc42, Rac1 and RhoA. We observe WNT-3a to differentially regulate small GTPase activity in platelets, promoting the GDP-bound form of Rap1b to inhibit integrin-α(IIb)β(3) adhesion, while concomitantly increasing Cdc42 and Rac1-GTP levels thereby disrupting normal platelet spreading. We demonstrate that Daam-1 interacts with Dishevelled upon platelet activation, which correlates with increased RhoA-GTP levels. Upon pre-treatment with WNT-3a, this complex disassociates, concurrent with a reduction in RhoA-GTP. Together these data implicate WNT-3a as a novel upstream regulator of small GTPase activity in platelets.
Original languageEnglish
Pages (from-to)2267-72
Number of pages6
JournalFEBS Letters
Volume586
Issue number16
DOIs
Publication statusPublished - 30 Jul 2012

Bibliographical note

Copyright © 2012 Federation of European Biochemical Societies. All rights reserved.

Keywords

  • Recombinant Proteins
  • Humans
  • Wnt3A Protein
  • rap GTP-Binding Proteins
  • Hydrolysis
  • Models, Biological
  • Guanosine Triphosphate
  • Blood Platelets
  • Adaptor Proteins, Signal Transducing
  • Extracellular Matrix
  • rac1 GTP-Binding Protein
  • Gene Expression Regulation
  • Monomeric GTP-Binding Proteins
  • cdc42 GTP-Binding Protein
  • Signal Transduction
  • Densitometry

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  • Cite this

    Steele, B. M., Harper, M. T., Smolenski, A. P., Alkazemi, N., Poole, A. W., Fitzgerald, D. J., & Maguire, P. B. (2012). WNT-3a modulates platelet function by regulating small GTPase activity. FEBS Letters, 586(16), 2267-72. https://doi.org/10.1016/j.febslet.2012.05.060