Type

Other / n/a

Authors

Michael C Berndt
R K Andrews
Dermot Kenny
Lorraine Coleman
E E Gardiner
Y Shen
J F Arthur

Subjects

Chemistry

Topics
reactive oxygen species traf4 glycoprotein vi glycoprotein ib ix v platelets redox life sciences nadph oxidase

TNF Receptor-Associated Factor 4 (TRAF4) is a novel binding partner of glycoprotein Ib and glycoprotein VI in human platelets. (2010)

Abstract Background: Reactive oxygen species generation is one consequence of ligand engagement of platelet glycoprotein (GP) receptors GPIb-IX-V and GPVI, which bind VWF/collagen and initiate thrombosis at arterial shear, however the precise molecular mechanism coupling redox pathway activation to engagement of these receptors is unknown. Objective: The objective of this study was to identify novel binding partners for GPIb-IX-V and GPVI that could provide a potential link between redox pathways and early platelet signalling events. Methods and Results: Using protein array analysis and affinity-binding assays, we demonstrated that the orphan TNF receptor-associated factor (TRAF) family member, TRAF4, selectively binds cytoplasmic sequences of GPIb╬▓ and GPVI. TRAF4, p47(phox) (of the NADPH oxidase (Nox2) enzyme complex), and other redox relevant signalling proteins such as Hic-5, co-immunoprecipitate with GPIb/GPVI from human platelet lysates whilst MBP-TRAF4 or MBP-p47(phox) fusion proteins specifically pull-down GPIb/GPVI. GPIb- or GPVI-selective agonists induce phosphorylation of the TRAF4-associated proteins, Hic-5 and Pyk2, with phosphorylation attenuated by Nox2 inhibition. Conclusion: These results describe the first direct association of TRAF4 with a receptor, and identify a novel binding partner for GPIb-IX-V and GPVI, providing a potential link between these platelet receptors and downstream TRAF4/Nox2-dependent redox pathways.
Collections Ireland -> Royal College of Surgeons in Ireland -> Department of Molecular and Cellular Therapeutics
Ireland -> Royal College of Surgeons in Ireland -> Molecular and Cellular Therapeutics Articles

Full list of authors on original publication

Michael C Berndt, R K Andrews, Dermot Kenny, Lorraine Coleman, E E Gardiner, Y Shen, J F Arthur

Experts in our system

1
Michael C Berndt
Royal College of Surgeons in Ireland
Total Publications: 12
 
2
Robert K Andrews
Royal College of Surgeons in Ireland
Total Publications: 4
 
3
Dermot Kenny
Royal College of Surgeons in Ireland
 
4
Elizabeth E Gardiner
Royal College of Surgeons in Ireland
Total Publications: 4