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November 28, 2002Journal of Biological ChemistryOpen Access

Coordinated Signaling through Both G12/13 and Gi Pathways Is Sufficient to Activate GPIIb/IIIa in Human Platelets

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Population

Human platelets

Comparison

Co-activation of G12/13 and Gi signaling pathways vs Activation of G12/13 or Gi pathways alone, or…

Design

Preclinical

Authors

RDRobert T. DorsamSKSoochong KimJJJianguo Jin

Discussion

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Overview

Calcium-dependent platelet activation by G12/13-Gi co-stimulation is mechanistically sufficient; leaves open in vivo relevance and therapeutic targeting.

Structured PICO

P
Population
Human platelets
I
Intervention
Co-activation of G12/13 and Gi signaling pathways (using YFLLRNP or thromboxane A2 mimetic combined with P2Y12 or alpha2A-adrenergic receptor stimulation)
C
Comparator
Activation of G12/13 or Gi pathways alone, or co-stimulation of Gq and Gi pathways
O
Outcome
Platelet GPIIb/IIIa activation (measured by platelet aggregation and PAC-1 binding)surrogate

Coordinated signaling through both G12/13 and Gi pathways is sufficient to activate the GPIIb/IIIa receptor in human platelets via an intracellular calcium-dependent mechanism.

Cite This Study

Dorsam et al. (2002) studied this question.

synapsesocial.com/papers/6a7624a9756843cacbb24df0https://doi.org/10.1074/jbc.m208778200
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Differential requirements for calcium and Src family kinases in platelet GPIIb/IIIa activation and thromboxane generation downstream of different G-protein pathways2004 · 44 citations
  2. 2Unresponsiveness of Platelets Lacking Both Gαq and Gα132004 · 70 citations
  3. 3GPIbα-selective activation of platelets induces platelet signaling events comparable to GPVI activation events2010 · 51 citations
  4. 4GPIb-dependent platelet activation is dependent on Src kinases but not MAP kinase or cGMP-dependent kinase2003 · 81 citations
  5. 5PAK Membrane Translocation and Phosphorylation Regulate Platelet Aggregation Downstream of Gi and G12/13 Pathways2020 · 5 citations