Dataset Information

Protein kinase C? and protein kinase C? double-deficient mice have a bleeding diathesis.

ABSTRACT:

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 PKC? 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 PKC?.

Results

PKC? 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 PKC?. 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 PKC? in supporting platelet activation under shear conditions and demonstrate that, in combination, the two novel PKCs support platelet activation.

SUBMITTER: Unsworth AJ

PROVIDER: S-EPMC3532618 | biostudies-literature | 2012 Sep

REPOSITORIES: biostudies-literature

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Publications

Protein kinase Cε and protein kinase Cθ double-deficient mice have a bleeding diathesis.

Unsworth A J AJ Finney B A BA Navarro-Nunez L L Severin S S Watson S P SP Pears C J CJ

Journal of thrombosis and haemostasis : JTH 20120901 9

<h4>Background</h4>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.<h4>Objectives</h4>To measure the levels of PKCθ and PKCε and to investigate the phenotype of mice deficient in both novel PKC isoforms.<h4>Methods</h4>Tail bleeding and platelet activation assays were monitored in mice and platelets from mice deficient in both PKCθ and PKCε.<h4>Results</h4>P ...[more]

PMID: 22812584

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