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October 7, 2005BloodOpen Access

Sequential activation of p38 and ERK pathways by cGMP-dependent protein kinase leading to activation of the platelet integrin αIIbβ3

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Population

cGMP-dependent protein kinase (PKG)-knockout mouse platelets and human platelets

Design

Preclinical

Authors

ZLZhenyu LiHebei Medical UniversityGZGuoying ZhangNSF NCAR High Altitude ObservatoryRFRobert FeilVascular / Pulmonary Vascular

Discussion

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Implication

p38 inhibition may attenuate aggregation in animal platelets; leaves open translation to human antithrombotic strategies.

Structured PICO

P
Population
cGMP-dependent protein kinase (PKG)-knockout mouse platelets and human platelets
I
Intervention
p38 inhibitors, dominant-negative mutant of p38 (p38AF), and PKG inhibitors
O
Outcome
Integrin alphaIIb beta3 activation and platelet aggregationsurrogate

This study delineates a novel signaling pathway in platelets where agonists sequentially activate PKG, p38, and ERK to induce integrin activation and aggregation.

Cite This Study

Li et al. (2005) studied this question.

synapsesocial.com/papers/6a6ff6b0660549caf2c48422https://doi.org/10.1182/blood-2005-03-1308
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Also Consider

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

  1. 1Negative Regulation of Mitogen-activated Protein Kinase Activation by Integrin αIIbβ3 in Platelets1997 · 51 citations
  2. 2cGMP-Dependent Protein Kinase I Mediates the Negative Inotropic Effect of cGMP in the Murine Myocardium2002 · 172 citations
  3. 3Adhesion receptor activation of phosphatidylinositol 3-kinase. von Willebrand factor stimulates the cytoskeletal association and activation of phosphatidylinositol 3-kinase and pp60c-src in human platelets.1994 · 127 citations
  4. 4Thrombin Induces Activation of p38 MAP Kinase in Human Platelets1995 · 216 citations
  5. 5Role of Fc receptor γ-chain in platelet glycoprotein Ib–mediated signaling2001 · 126 citations