Platelets undergo phosphorylation of Syk at Y525/526 and Y352 in response to pathophysiological shear stress

American Journal of Physiology. Cell Physiology
Henry E SpeichLisa K Jennings

Abstract

Atherosclerotic plaques can lead to partial vascular occlusions that produce abnormally high levels of arterial wall shear stress. Such pathophysiological shear stress can promote shear-induced platelet aggregation (SIPA), which has been linked to acute myocardial infarction, unstable angina, and stroke. This study investigated the role of the tyrosine kinase Syk in shear-induced human platelet signaling. The extent of Syk tyrosine phosphorylation induced by pathophysiological levels of shear stress (100 dyn/cm(2)) was significantly greater than that resulting from physiological shear stress (10 dyn/cm(2)). With the use of phospho-Syk specific antibodies, these data are the first to show that key regulatory sites of Syk at tyrosines 525/526 (Y525/526) and tyrosine 352 (Y352) were phosphorylated in response to pathophysiological shear stress. Increased phosphorylation at both sites was attenuated by pharmacological inhibition of Syk using two different Syk inhibitors, piceatannol and 3-(1-methyl-1H-indol-3-yl-methylene)-2-oxo-2,3-dihydro-1H-indole-5-sulfonamide (OXSI-2), and by inhibition of upstream Src-family kinases (SFKs). Shear-induced response at the Syk 525/526 site was ADP dependent but not contingent on glycoprotein (GP...Continue Reading

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Citations

Oct 18, 2012·Journal of Thrombosis and Thrombolysis·Henry E SpeichLisa K Jennings
Jan 24, 2013·The Journal of Biological Chemistry·Bhanu Kanth ManneSatya P Kunapuli
Oct 29, 2008·Hematology/oncology Clinics of North America·Luca PaoluzziOwen A O'Connor
Jun 25, 2009·Journal of Thrombosis and Haemostasis : JTH·H E SpeichL K Jennings
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Mar 15, 2018·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Chen QuJian Hong
Jul 3, 2018·Blood Coagulation & Fibrinolysis : an International Journal in Haemostasis and Thrombosis·Khon HuynhVolker R Stoldt
Sep 18, 2012·The Journal of Pharmacology and Experimental Therapeutics·Keunyoung KimJin-Ho Chung

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