Effects of thrombin on interactions between beta3-integrins and extracellular matrix in platelets and vascular cells.
The beta3-integrin family consists of alphaIIbbeta3 (also known as glycoprotein IIb/IIIa) and alpha(v)beta3. alphaIIbbeta3 is found on platelets and megakaryocytes and has an essential role in hemostasis. alpha(v)beta3 has a broader distribution, and it functions in angiogenesis, neointimal formation after vascular injury, and leukocyte trafficking. There are important interactions between thrombin and beta3-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 alphaIIbbeta3. Conversely, outside-in signaling through alphaIIbbeta3 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)beta3-integrins influence various responses to thrombin, including proliferation, c-Jun NH2-terminal kinase-1 activation, and focal adhesion formation. Other interactions between beta3-integrins and thrombin include beta3-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 beta3-integrin function for platelet-dependent clot retraction. In summary, there is increasing evidence that interactions between beta3-integrins and thrombin play important roles in the regulation of hemostatic and vascular functions.
Stouffer
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Division of Cardiology and Carolina Cardiovascular Biology Center, University of North Carolina, Chapel Hill, NC 27599-7075, USA. rstouff@med.unc.edu
Smyth
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D000818:Animals; D001777:Blood Coagulation / Q000502:physiology; D001792:Blood Platelets / Q000378:metabolism*; D042783:Endothelial Cells / Q000378:metabolism*; D005109:Extracellular Matrix / Q000378:metabolism*; D006801:Humans; D039661:Integrin beta3 / Q000378:metabolism*; D015539:Platelet Activation / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D013917:Thrombin / Q000502:physiology*
D039661:Integrin beta3; D013917:Thrombin