Dok-1 negatively regulates platelet integrin αIIbβ3 outside-in signalling and inhibits thrombosis in mice

Thrombosis and Haemostasis
Masaru NikiSteven R Lentz

Abstract

Adaptor proteins play a critical role in the assembly of signalling complexes after engagement of platelet receptors by agonists such as collagen, ADP and thrombin. Recently, using proteomics, the Dok (downstream of tyrosine kinase) adapter proteins were identified in human and mouse platelets. In vitro studies suggest that Dok-1 binds to platelet integrin β3, but the underlying effects of Dok-1 on αIIbβ3 signalling, platelet activation and thrombosis remain to be elucidated. In the present study, using Dok-1-deficient (Dok-1-/-) mice, we determined the phenotypic role of Dok-1 in αIIbβ3 signalling. We found that platelets from Dok-1-/- mice displayed normal aggregation, activation of αIIbβ3 (assessed by binding of JON/A), P-selectin surface expression (assessed by anti-CD62P), and soluble fibrinogen binding. These findings indicate that Dok-1 does not affect "inside-out" platelet signalling. Compared with platelets from wild-type (WT) mice, platelets from Dok-1-/- mice exhibited increased clot retraction (p < 0.05 vs WT), increased PLCγ2 phosphorylation, and enhanced spreading on fibrinogen after thrombin stimulation (p < 0.01 vs WT), demonstrating that Dok-1 negatively regulates αIIbβ3 "outside-in" signalling. Finally, we fou...Continue Reading

References

Jul 1, 1980·The Journal of Cell Biology·D R PhillipsH H Edwards
Apr 20, 2002·Cellular and Molecular Life Sciences : CMLS·I P Casserly, E J Topol
Feb 28, 2003·Proceedings of the National Academy of Sciences of the United States of America·David A CalderwoodMark H Ginsberg
Jul 2, 2003·The Journal of Biological Chemistry·Peter WonerowSteve P Watson
Dec 17, 2003·Journal of Thrombosis and Haemostasis : JTH·K M WilsonS R Lentz
Jun 19, 2004·Blood·Sanford J Shattil, Peter J Newman
Dec 22, 2004·The Journal of Experimental Medicine·Masaru NikiPier Paolo Pandolfi
Aug 16, 2005·Current Opinion in Cell Biology·Mark H GinsbergSanford J Shattil
Oct 1, 2005·The Journal of Biological Chemistry·Owen J T McCartySteve P Watson
Oct 24, 2006·Thrombosis Research·Katsue Suzuki-InoueYukio Ozaki
Jan 16, 2007·Cell·Kate L WegenerIain D Campbell
Jul 20, 2007·Journal of Thrombosis and Haemostasis : JTH·Y-Q MaE F Plow
Dec 25, 2007·The Journal of Biological Chemistry·Camilla L OxleyKate L Wegener
May 7, 2008·The Journal of Cell Biology·Yan-Qing MaEdward F Plow
Jan 2, 2009·Journal of Cell Science·Kyle R Legate, Reinhard Fässler
Feb 24, 2009·Nature Medicine·Markus MoserReinhard Fässler
Jun 26, 2009·Current Opinion in Hematology·Edward F PlowTatiana Byzova
Oct 22, 2009·The Journal of Biological Chemistry·Nicholas J AnthisIain D Campbell
Mar 24, 2010·Nature Reviews. Molecular Cell Biology·Sanford J ShattilMark H Ginsberg

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Citations

Aug 11, 2017·Blood·Tom N DurrantIngeborg Hers
Dec 2, 2017·Journal of Thrombosis and Haemostasis : JTH·L Stefanini, W Bergmeier
Mar 9, 2019·Journal of Hematology & Oncology·Jiansong HuangJie Jin

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