NDLI: Key role of integrin αIIbβ3 signaling to Syk kinase in tissue factor-induced thrombin generation

Content Provider	Springer Nature Link
Author	Meijden, Paola E. J. Feijge, Marion A. H. Swieringa, Frauke Gilio, Karen Nergiz Unal, Reyhan Hamulyák, Karly Heemskerk, Johan W. M.
Copyright Year	2012
Abstract	The fibrin(ogen) receptor, integrin αIIbβ3, has a well-established role in platelet spreading, aggregation and clot retraction. How αIIbβ3 contributes to platelet-dependent coagulation is less well resolved. Here, we demonstrate that the potent suppressing effect of clinically used αIIbβ3 blockers on tissue factor-induced thrombin generation is linked to diminished platelet Ca2+ responses and phosphatidylserine (PS) exposure. The same blockers suppress these responses in platelets stimulated with collagen and thrombin receptor agonists, whereas added fibrinogen potentiates these responses. In platelets spreading on fibrinogen, outside-in αIIbβ3 signaling similarly enhances thrombin-induced Ca2+ rises and PS exposure. These responses are reduced in αIIbβ3-deficient platelets from patients with Glanzmann’s thrombasthenia. Furthermore, the contribution of αIIbβ3 to tissue factor-induced platelet Ca2+ rises, PS exposure and thrombin generation in plasma are fully dependent on Syk kinase activity. Tyrosine phosphorylation analysis confirms a key role of Syk activation, which is largely but not exclusively dependent on αIIbβ3 activation. It is concluded that the majority of tissue factor-induced procoagulant activity of platelets relies on Syk activation and ensuing Ca2+ signal generation, and furthermore that a considerable part of Syk activation relies on αIIbβ3 signaling. These results hence point to a novel role of Syk in integrin-dependent thrombin generation.
Starting Page	3481
Ending Page	3492
Page Count	12
File Format	PDF
ISSN	1420682X
Journal	Cellular and Molecular Life Sciences
Volume Number	69
Issue Number	20
e-ISSN	14209071
Language	English
Publisher	SP Birkhäuser Verlag Basel
Publisher Date	2012-06-06
Publisher Place	Basel
Access Restriction	Subscribed
Subject Keyword	Platelets Integrin αIIbβ3 Thrombin generation Syk kinase PS exposure Biomedicine general Cell Biology Life Sciences Biochemistry
Content Type	Text
Resource Type	Article
Subject	Cell Biology Molecular Biology Molecular Medicine Pharmacology Cellular and Molecular Neuroscience

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1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
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7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
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9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

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