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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

A schematic structure of platelet integrin αIIbβ3. The αIIb subunit is composed of a heavy and a light chain. The light chain contains a cytoplasmic tail, a transmembrane helix, and an extracellular segment that is disulfide linked to the heavy chain, which is entirely extracellular. The β3 subunit is a single polypeptide chain. The 2 subunits assemble into the divalent, cation-dependent heterodimer.
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Figure 2: A schematic structure of platelet integrin αIIbβ3. The αIIb subunit is composed of a heavy and a light chain. The light chain contains a cytoplasmic tail, a transmembrane helix, and an extracellular segment that is disulfide linked to the heavy chain, which is entirely extracellular. The β3 subunit is a single polypeptide chain. The 2 subunits assemble into the divalent, cation-dependent heterodimer.

Mentions: Integrin αIIbβ3 is present 60,000-80,000 copies per resting platelet, which is the highest density of all platelet membrane proteins. The membranes of platelet α-granules contain αIIbβ3 that becomes externalized on platelet secretion to increase the surface expression of αIIbβ3 by 25% to 50%. The αIIb subunit consists of 1008 amino acids, which is composed of a heavy and a light chain. The light chain contains a 20-amino acid cytoplasmic tail, a transmembrane helix, and an extracellular segment that is a disulfide linked to the heavy chain, which is entirely extracellular. The β3 subunit is a single polypeptide chain of 762 amino acids. The 2 subunits assemble into the divalent, cation-dependent heterodimer during biosynthesis in megakaryocytes (Fig. 2).17)18)


Mechanisms of Platelet Activation and Integrin αIIβ3.

Joo SJ - Korean Circ J (2012)

A schematic structure of platelet integrin αIIbβ3. The αIIb subunit is composed of a heavy and a light chain. The light chain contains a cytoplasmic tail, a transmembrane helix, and an extracellular segment that is disulfide linked to the heavy chain, which is entirely extracellular. The β3 subunit is a single polypeptide chain. The 2 subunits assemble into the divalent, cation-dependent heterodimer.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 2: A schematic structure of platelet integrin αIIbβ3. The αIIb subunit is composed of a heavy and a light chain. The light chain contains a cytoplasmic tail, a transmembrane helix, and an extracellular segment that is disulfide linked to the heavy chain, which is entirely extracellular. The β3 subunit is a single polypeptide chain. The 2 subunits assemble into the divalent, cation-dependent heterodimer.
Mentions: Integrin αIIbβ3 is present 60,000-80,000 copies per resting platelet, which is the highest density of all platelet membrane proteins. The membranes of platelet α-granules contain αIIbβ3 that becomes externalized on platelet secretion to increase the surface expression of αIIbβ3 by 25% to 50%. The αIIb subunit consists of 1008 amino acids, which is composed of a heavy and a light chain. The light chain contains a 20-amino acid cytoplasmic tail, a transmembrane helix, and an extracellular segment that is a disulfide linked to the heavy chain, which is entirely extracellular. The β3 subunit is a single polypeptide chain of 762 amino acids. The 2 subunits assemble into the divalent, cation-dependent heterodimer during biosynthesis in megakaryocytes (Fig. 2).17)18)

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