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- Title
WNT-3a modulates platelet function by regulating small GTPase activity
- Authors
Steele, Brian M.; Harper, Matthew T.; Smolenski, Albert P.; Alkazemi, Naheda; Poole, Alastair W.; Fitzgerald, Desmond J.; Maguire, Patricia B.
- Abstract
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-αIIbβ3 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. Structured summary of protein interactions: DVL physically interacts with DAAM-1 by anti bait co-immunoprecipitation (View interaction) DVL and DAAM-1 colocalise by fluorescence microscopy (View interaction)
- Subjects
WNT proteins; GENETIC regulation; GTPASE-activating protein; CELL adhesion; BLOOD platelet activation; PROTEIN-protein interactions
- Publication
FEBS Letters, 2012, Vol 586, Issue 16, p2267
- ISSN
0014-5793
- Publication type
Article
- DOI
10.1016/j.febslet.2012.05.060