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Multiple ways to switch platelet integrins on and off
Author(s) -
COSEMANS J. M. E. M.,
ISERBYT B. F.,
DECKMYN H.,
HEEMSKERK J. W. M.
Publication year - 2008
Publication title -
journal of thrombosis and haemostasis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.947
H-Index - 178
eISSN - 1538-7836
pISSN - 1538-7933
DOI - 10.1111/j.1538-7836.2008.03041.x
Subject(s) - integrin , platelet , gpvi , platelet activation , microbiology and biotechnology , thrombin , collagen receptor , chemistry , alpha (finance) , stimulation , beta (programming language) , clot retraction , platelet adhesiveness , integrin, beta 6 , fibrin , receptor , immunology , biology , medicine , biochemistry , endocrinology , platelet aggregation , construct validity , nursing , patient satisfaction , computer science , programming language
Summary. In the classical concept of platelet integrin activation, it is considered that unidirectional conformational changes of α IIb β 3 and α 2 β 1 regulate the adhesiveness of platelets for fibrin(ogen) and collagen, respectively. Here, we summarize recent evidence that these conformational changes: (i) can also occur in the reverse direction; and (ii) are not independent events. Platelet stimulation through the P2Y 12 receptors provokes only transient α IIb β 3 activation via signaling routes involving phosphoinositide 3‐kinases and Rap1b. Furthermore, α IIb β 3 can be secondarily inactivated in platelets with prolonged high Ca 2+ rises, which expose phosphatidylserine and bind coagulation factors. Thus, platelet stimulation with strong agonists (collagen and thrombin) also results in transient integrin activation. Integrin α 2 β 1 is found to be activated by a mechanism that is directly linked to α IIb β 3 activation. Integrin α 2 β 1 can adopt different activation states, depending on the trigger. Conclusively, reversibility and synchrony of platelet integrin activation are newly identified mechanisms to restrict thrombus growth and to allow optimal coagulation factor binding. Back‐shifting of activated integrins towards their resting state may be a novel goal of antithrombotic medication.