Multiple ways to switch platelet integrins on and off

J Thromb Haemost. 2008 Aug;6(8):1253-61. doi: 10.1111/j.1538-7836.2008.03041.x. Epub 2008 May 28.


In the classical concept of platelet integrin activation, it is considered that unidirectional conformational changes of alpha(IIb)beta(3) and alpha(2)beta(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 alpha(IIb)beta(3) activation via signaling routes involving phosphoinositide 3-kinases and Rap1b. Furthermore, alpha(IIb)beta(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 alpha(2)beta(1) is found to be activated by a mechanism that is directly linked to alpha(IIb)beta(3) activation. Integrin alpha(2)beta(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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Blood Platelets / physiology*
  • Humans
  • Integrin alpha2beta1 / blood
  • Integrin alpha2beta1 / chemistry
  • Integrin alpha2beta1 / physiology
  • Integrins / blood*
  • Integrins / chemistry
  • Integrins / physiology
  • Platelet Activation / physiology
  • Platelet Adhesiveness / physiology
  • Platelet Aggregation / physiology
  • Platelet Glycoprotein GPIIb-IIIa Complex / chemistry
  • Platelet Glycoprotein GPIIb-IIIa Complex / physiology
  • Protein Conformation
  • Receptors, Purinergic P2 / blood
  • Receptors, Purinergic P2 / physiology
  • Receptors, Purinergic P2Y12
  • Signal Transduction
  • Thrombosis / blood
  • Thrombosis / etiology


  • Integrin alpha2beta1
  • Integrins
  • P2RY12 protein, human
  • Platelet Glycoprotein GPIIb-IIIa Complex
  • Receptors, Purinergic P2
  • Receptors, Purinergic P2Y12