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

Molecular mechanisms involved in the activation of integrin αIIbβ3. G protein-mediated signaling pathways, which are initiated by Gq or Gi, include phospholipase C with calcium signaling, protein kinase C (PKC) and phosphatidylinositol 3-kinase (PI-3K). Rap1b, Ca2+ and diacylglycerol-regulated guanine nucleotide exchange factor I (CalDAG-GEFI), Rap1-GTP-interacting adaptor molecule (RIAM), and Akt are important molecules 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. AC: adenylyl cyclase, CRAC: Ca2+ release activated calcium channel, ER: endoplasmic reticulum, GSK: glycogen synthase kinase, IP3: inositol 1,4,5-triphosphate, IP3R: IP3 receptor, NOS3: nitric oxide synthase 3, PDE: phosphodiesterase, PIP2: phosphoinositol biphosphate.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 4: Molecular mechanisms involved in the activation of integrin αIIbβ3. G protein-mediated signaling pathways, which are initiated by Gq or Gi, include phospholipase C with calcium signaling, protein kinase C (PKC) and phosphatidylinositol 3-kinase (PI-3K). Rap1b, Ca2+ and diacylglycerol-regulated guanine nucleotide exchange factor I (CalDAG-GEFI), Rap1-GTP-interacting adaptor molecule (RIAM), and Akt are important molecules 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. AC: adenylyl cyclase, CRAC: Ca2+ release activated calcium channel, ER: endoplasmic reticulum, GSK: glycogen synthase kinase, IP3: inositol 1,4,5-triphosphate, IP3R: IP3 receptor, NOS3: nitric oxide synthase 3, PDE: phosphodiesterase, PIP2: phosphoinositol biphosphate.

Mentions: The activation mechanism of integrin αIIbβ3 from a low- to high-affinity state has been intensively studied because this signal transduction pathway may be a potential target for a new antithrombotic agent. Conformational changes of the extracellular domains of integrin αIIbβ3 and resulting affinity modulation are initiated by the interaction at the cytoplasmic tails. Cellular control of integrin activation requires transmission of a signal from the small cytoplasmic tails to the large extracellular domains. The exact mechanism involved in inside-out and outside-in signaling of integrin αIIbβ3 is not fully understood, and the functional significance of the related proteins is still evolving (Fig. 4).10)16)


Mechanisms of Platelet Activation and Integrin αIIβ3.

Joo SJ - Korean Circ J (2012)

Molecular mechanisms involved in the activation of integrin αIIbβ3. G protein-mediated signaling pathways, which are initiated by Gq or Gi, include phospholipase C with calcium signaling, protein kinase C (PKC) and phosphatidylinositol 3-kinase (PI-3K). Rap1b, Ca2+ and diacylglycerol-regulated guanine nucleotide exchange factor I (CalDAG-GEFI), Rap1-GTP-interacting adaptor molecule (RIAM), and Akt are important molecules 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. AC: adenylyl cyclase, CRAC: Ca2+ release activated calcium channel, ER: endoplasmic reticulum, GSK: glycogen synthase kinase, IP3: inositol 1,4,5-triphosphate, IP3R: IP3 receptor, NOS3: nitric oxide synthase 3, PDE: phosphodiesterase, PIP2: phosphoinositol biphosphate.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 4: Molecular mechanisms involved in the activation of integrin αIIbβ3. G protein-mediated signaling pathways, which are initiated by Gq or Gi, include phospholipase C with calcium signaling, protein kinase C (PKC) and phosphatidylinositol 3-kinase (PI-3K). Rap1b, Ca2+ and diacylglycerol-regulated guanine nucleotide exchange factor I (CalDAG-GEFI), Rap1-GTP-interacting adaptor molecule (RIAM), and Akt are important molecules 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. AC: adenylyl cyclase, CRAC: Ca2+ release activated calcium channel, ER: endoplasmic reticulum, GSK: glycogen synthase kinase, IP3: inositol 1,4,5-triphosphate, IP3R: IP3 receptor, NOS3: nitric oxide synthase 3, PDE: phosphodiesterase, PIP2: phosphoinositol biphosphate.
Mentions: The activation mechanism of integrin αIIbβ3 from a low- to high-affinity state has been intensively studied because this signal transduction pathway may be a potential target for a new antithrombotic agent. Conformational changes of the extracellular domains of integrin αIIbβ3 and resulting affinity modulation are initiated by the interaction at the cytoplasmic tails. Cellular control of integrin activation requires transmission of a signal from the small cytoplasmic tails to the large extracellular domains. The exact mechanism involved in inside-out and outside-in signaling of integrin αIIbβ3 is not fully understood, and the functional significance of the related proteins is still evolving (Fig. 4).10)16)

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