Journal
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
Volume 10, Issue 9, Pages 1887-1894Publisher
WILEY
DOI: 10.1111/j.1538-7836.2012.04857.x
Keywords
aggregation; bleeding times; collagen; fibrinogen; hemostasis; protein kinase C
Categories
Funding
- British Heart Foundation (BHF) [FS/08/010/24527]
- Spanish Ministry of Education [EX2009-0242]
- Wellcome Trust
- British Heart Foundation [PG/11/119/29299] Funding Source: researchfish
- Medical Research Council [G9818340B] Funding Source: researchfish
Ask authors/readers for more resources
. Background: In comparison to the classical isoforms of protein kinase C (PKC), the novel isoforms are thought to play minor or inhibitory roles in the regulation of platelet activation and thrombosis. Objectives: To measure the levels of PKC? and PKCe and to investigate the phenotype of mice deficient in both novel PKC isoforms. Methods: Tail bleeding and platelet activation assays were monitored in mice and platelets from mice deficient in both PKC? and PKCe. Results: PKCe plays a minor role in supporting aggregation and secretion following stimulation of the collagen receptor GPVI in mouse platelets but has no apparent role in spreading on fibrinogen. PKC?, in contrast, plays a minor role in supporting adhesion and filopodial generation on fibrinogen but has no apparent role in aggregation and secretion induced by GPVI despite being expressed at over 10 times the level of PKCe. Platelets deficient in both novel isoforms have a similar pattern of aggregation downstream of GPVI and spreading on fibrinogen as the single null mutants. Strikingly, a marked reduction in aggregation on collagen under arteriolar shear conditions is observed in blood from the double but not single-deficient mice along with a significant increase in tail bleeding. Conclusions: These results reveal a greater than additive role for PKC? and PKCe in supporting platelet activation under shear conditions and demonstrate that, in combination, the two novel PKCs support platelet activation.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available