Effects of thrombin on interactions between beta 3-integrins and extracellular matrix in platelets and vascular cells

The beta(3)- integrin family consists of alpha(IIb)beta(3) ( also known as glycoprotein IIb/ IIIa) and alpha(v)beta(3). alpha(IIb)beta(3) is found on platelets and megakaryocytes and has an essential role in hemostasis. alpha(v)beta(3) has a broader distribution, and it functions in angiogenesis, neointimal formation after vascular injury, and leukocyte trafficking. There are important interactions between thrombin and beta(3)- integrins relative to both inside- out ( integrin activation) and outside- in ( modification of cellular events by ligand binding to integrins) signaling. Thrombin, by binding to G protein - coupled, protease- activated receptors, is a potent activator of alpha(IIb)beta(3). Conversely, outside- in signaling through alpha(IIb)beta(3) amplifies events initiated by thrombin and is necessary for full platelet spreading, platelet aggregation, granule secretion, and the formation of a stable platelet thrombus. In smooth muscle cells, alpha(v)beta(3)- integrins influence various responses to thrombin, including proliferation, c- Jun NH2- terminal kinase- 1 activation, and focal adhesion formation. Other interactions between beta(3)- integrins and thrombin include beta(3)- integrin promotion of the generation of thrombin by localizing prothrombin to cellular surfaces and/ or enhancing the formation of procoagulant microparticles and the requirement of beta(3)- integrin function for platelet- dependent clot retraction. In summary, there is increasing evidence that interactions between beta(3)- integrins and thrombin play important roles in the regulation of hemostatic and vascular functions.