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 |
| |
Institution: | UCD Conway Institute, University College Dublin, Belfield, Dublin D4, Ireland. brian.steele@ucd.ie |
| |
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. |
| |
Keywords: | |
本文献已被 ScienceDirect PubMed 等数据库收录! |
|