Limits...
Mechanisms of Platelet Activation and Integrin αIIβ3.

Joo SJ - Korean Circ J (2012)

Bottom Line: G protein-mediated signaling pathways, which are initiated by G(q), G(12)/G(13) or G(i), include phospholipase C with calcium signaling, Rho signaling, protein kinase C and phosphatidylinositol 3-kinase.Rap1b, Ca(2+) and diacylglycerol-regulated guanine nucleotide exchange factor I, Rap1-GTP-interacting adaptor molecule, and Akt are important proteins involved in G protein-mediated activation of integrin αIIbβ3.Binding of talin-1 and kindlin-3 to cytoplasmic domains of β3-integrin triggers a conformational change in the extracellular domains that increases its affinity for ligands, such as fibrinogen or von Willebrand factor.

View Article: PubMed Central - PubMed

Affiliation: Cardiology Division, Department of Internal Medicine, Jeju National University Hospital, Jeju, Korea.

ABSTRACT
Platelet aggregation is not only an essential part of hemostasis, but also initiates acute coronary syndrome or ischemic stroke. The precise understanding of the activation mechanism of platelet aggregation is fundamental for the development of more effective agents against platelet aggregation. Adenosine diphosphate, thrombin, and thromboxane A(2) activate platelet integrin αIIbβ3 through G protein-coupled receptors. G protein-mediated signaling pathways, which are initiated by G(q), G(12)/G(13) or G(i), include phospholipase C with calcium signaling, Rho signaling, protein kinase C and phosphatidylinositol 3-kinase. Rap1b, Ca(2+) and diacylglycerol-regulated guanine nucleotide exchange factor I, Rap1-GTP-interacting adaptor molecule, and Akt are important proteins involved in G protein-mediated activation of integrin αIIbβ3. Binding of talin-1 and kindlin-3 to cytoplasmic domains of β3-integrin triggers a conformational change in the extracellular domains that increases its affinity for ligands, such as fibrinogen or von Willebrand factor. Fibrinogens act as bridges between adjacent platelets to generate a platelet aggregate.

No MeSH data available.


Related in: MedlinePlus

"Inside-out" and "outside-in" signaling of integrin αIIbβ3. A: platelet adhesion to extracellular matrix, or agonists, such as ADP, thrombin, or arachidonic acid, initiate platelet activation process that requires transmission of information from within the cell to the extracellular domain of αIIbβ3, a process referred to as "inside-out" signaling, which changes receptors from a low- to high-affinity state. B: ligand-occupied integrin αIIbβ3 triggers various cellular processes within platelets, through "outside-in" signaling.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC3369959&req=5

Figure 3: "Inside-out" and "outside-in" signaling of integrin αIIbβ3. A: platelet adhesion to extracellular matrix, or agonists, such as ADP, thrombin, or arachidonic acid, initiate platelet activation process that requires transmission of information from within the cell to the extracellular domain of αIIbβ3, a process referred to as "inside-out" signaling, which changes receptors from a low- to high-affinity state. B: ligand-occupied integrin αIIbβ3 triggers various cellular processes within platelets, through "outside-in" signaling.

Mentions: The ligands of αIIbβ3 include fibrinogen, fibronectin, von Willebrand factor, and vitronectin. Fibrinogen and von Willebrand factor support platelet aggregation. Integrin αIIbβ3 recognizes Arg-Gly-Asp (RGD) sequence of the ligands. The most important characteristic of integrin αIIbβ3 is the affinity modulation after its activation. In resting platelets, the affinity of αIIbβ3 for fibrinogen, a main ligand of platelet aggregation, is low, and minimal binding occurs despite the high levels of fibrinogen in blood. Activation of integrin αIIbβ3 depends primarily on the conformational change of the receptors, whether induced by platelet adhesion to extracellular matrix, or agonists, such as ADP, thrombin, or arachidonic acid. This requires transmission of information from within the cell to the extracellular domain of αIIbβ3, a process referred to as "inside-out" signaling, which changes receptors from a low- to high-affinity state (Fig. 3A). Integrin activation can involve changes not only in affinity for ligand, but also in avidity for ligand, a consequence of receptor clustering. Both mechanisms can lead to activation of αIIbβ3, but affinity modulation is dominant. Platelet activation leads to a marked increase in the affinity of αIIbβ3 for fibrinogen. Ligand-occupied integrin αIIbβ3, on the other hand, triggers various cellular processes, such as reorganization of the cytoskeleton within platelets, through "outside-in" signaling (Fig. 3B).17)


Mechanisms of Platelet Activation and Integrin αIIβ3.

Joo SJ - Korean Circ J (2012)

"Inside-out" and "outside-in" signaling of integrin αIIbβ3. A: platelet adhesion to extracellular matrix, or agonists, such as ADP, thrombin, or arachidonic acid, initiate platelet activation process that requires transmission of information from within the cell to the extracellular domain of αIIbβ3, a process referred to as "inside-out" signaling, which changes receptors from a low- to high-affinity state. B: ligand-occupied integrin αIIbβ3 triggers various cellular processes within platelets, through "outside-in" signaling.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3369959&req=5

Figure 3: "Inside-out" and "outside-in" signaling of integrin αIIbβ3. A: platelet adhesion to extracellular matrix, or agonists, such as ADP, thrombin, or arachidonic acid, initiate platelet activation process that requires transmission of information from within the cell to the extracellular domain of αIIbβ3, a process referred to as "inside-out" signaling, which changes receptors from a low- to high-affinity state. B: ligand-occupied integrin αIIbβ3 triggers various cellular processes within platelets, through "outside-in" signaling.
Mentions: The ligands of αIIbβ3 include fibrinogen, fibronectin, von Willebrand factor, and vitronectin. Fibrinogen and von Willebrand factor support platelet aggregation. Integrin αIIbβ3 recognizes Arg-Gly-Asp (RGD) sequence of the ligands. The most important characteristic of integrin αIIbβ3 is the affinity modulation after its activation. In resting platelets, the affinity of αIIbβ3 for fibrinogen, a main ligand of platelet aggregation, is low, and minimal binding occurs despite the high levels of fibrinogen in blood. Activation of integrin αIIbβ3 depends primarily on the conformational change of the receptors, whether induced by platelet adhesion to extracellular matrix, or agonists, such as ADP, thrombin, or arachidonic acid. This requires transmission of information from within the cell to the extracellular domain of αIIbβ3, a process referred to as "inside-out" signaling, which changes receptors from a low- to high-affinity state (Fig. 3A). Integrin activation can involve changes not only in affinity for ligand, but also in avidity for ligand, a consequence of receptor clustering. Both mechanisms can lead to activation of αIIbβ3, but affinity modulation is dominant. Platelet activation leads to a marked increase in the affinity of αIIbβ3 for fibrinogen. Ligand-occupied integrin αIIbβ3, on the other hand, triggers various cellular processes, such as reorganization of the cytoskeleton within platelets, through "outside-in" signaling (Fig. 3B).17)

Bottom Line: G protein-mediated signaling pathways, which are initiated by G(q), G(12)/G(13) or G(i), include phospholipase C with calcium signaling, Rho signaling, protein kinase C and phosphatidylinositol 3-kinase.Rap1b, Ca(2+) and diacylglycerol-regulated guanine nucleotide exchange factor I, Rap1-GTP-interacting adaptor molecule, and Akt are important proteins involved in G protein-mediated activation of integrin αIIbβ3.Binding of talin-1 and kindlin-3 to cytoplasmic domains of β3-integrin triggers a conformational change in the extracellular domains that increases its affinity for ligands, such as fibrinogen or von Willebrand factor.

View Article: PubMed Central - PubMed

Affiliation: Cardiology Division, Department of Internal Medicine, Jeju National University Hospital, Jeju, Korea.

ABSTRACT
Platelet aggregation is not only an essential part of hemostasis, but also initiates acute coronary syndrome or ischemic stroke. The precise understanding of the activation mechanism of platelet aggregation is fundamental for the development of more effective agents against platelet aggregation. Adenosine diphosphate, thrombin, and thromboxane A(2) activate platelet integrin αIIbβ3 through G protein-coupled receptors. G protein-mediated signaling pathways, which are initiated by G(q), G(12)/G(13) or G(i), include phospholipase C with calcium signaling, Rho signaling, protein kinase C and phosphatidylinositol 3-kinase. Rap1b, Ca(2+) and diacylglycerol-regulated guanine nucleotide exchange factor I, Rap1-GTP-interacting adaptor molecule, and Akt are important proteins involved in G protein-mediated activation of integrin αIIbβ3. Binding of talin-1 and kindlin-3 to cytoplasmic domains of β3-integrin triggers a conformational change in the extracellular domains that increases its affinity for ligands, such as fibrinogen or von Willebrand factor. Fibrinogens act as bridges between adjacent platelets to generate a platelet aggregate.

No MeSH data available.


Related in: MedlinePlus