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Involvement of Src kinases and PLCγ2 in clot retraction
- Source :
- Thrombosis Research
- Publication Year :
- 2007
- Publisher :
- Pergamon Press, 2007.
-
Abstract
- The integrin alpha(IIb)beta(3) plays a critical role in mediating clot retraction by platelets which is important in vivo in consolidating thrombus formation. Actin-myosin interaction is essential for clot retraction. In the present study, we demonstrate that the structurally distinct Src kinase inhibitors, PP2 and PD173952, significantly reduced the rate of clot retraction, but did not prevent it reaching completion. This effect was accompanied by abolition of alpha(IIb)beta(3)-dependent protein tyrosine phosphorylation, including PLCgamma2. A role for PLCgamma2 in mediating clot retraction was demonstrated using PLCgamma2-deficient murine platelets. Furthermore, platelet adhesion to fibrinogen leads to MLC phosphorylation through a pathway that is inhibited by PP2 and by the PLC inhibitor, U73122. These results demonstrate a partial role for Src kinase-dependent activation of PLCgamma2 and MLC phosphorylation in mediating clot retraction downstream of integrin alpha(IIb)beta(3).
- Subjects :
- 030204 cardiovascular system & hematology
Fibrinogen
PRP, platelet-rich plasma
chemistry.chemical_compound
Mice
0302 clinical medicine
PLCγ2, phospholipase Cγ2
Phosphorylation
TBS-T, Tris-buffered saline/Tween 20
0303 health sciences
Kinase
digestive, oral, and skin physiology
Regular Article
Hematology
ACD, acid/citrate/dextrose
3. Good health
Cell biology
Platelet Glycoprotein GPIIb-IIIa Complex
Integrin αIIbβ3
src-Family Kinases
SLP-76, SH2-containing leucocyte phosphoprotein of 76 kDa
Outside-in signal
Src kinases
Proto-oncogene tyrosine-protein kinase Src
medicine.drug
circulatory and respiratory physiology
Signal Transduction
Blood Platelets
Myosin Light Chains
PLCγ2
Integrin
Clot Retraction
Clot retraction
macromolecular substances
Biology
In Vitro Techniques
PP2, 4-amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo-d-3,4-pyrimidine
Models, Biological
03 medical and health sciences
medicine
Animals
Humans
mAb, monoclonal antibody
Protein Kinase Inhibitors
030304 developmental biology
Phospholipase C gamma
Tyrosine phosphorylation
Molecular biology
chemistry
biology.protein
Subjects
Details
- Language :
- English
- ISSN :
- 18792472 and 00493848
- Volume :
- 120
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- Thrombosis Research
- Accession number :
- edsair.doi.dedup.....48936df03a44d18f0f5ff7b89b4078cf