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Differential roles of the PKC novel isoforms, PKCδ and PKCε, in mouse and human platelets

Orgel, Joseph P.R.O., Pears, Catherine J., Thornber, Kelly, Auger, Jocelyn M., Hughes, Craig E., Grygielska, Beata, Protty, Majd B., Pearce, Andrew C. and Watson, Steve P. 2008. Differential roles of the PKC novel isoforms, PKCδ and PKCε, in mouse and human platelets. PLoS ONE 3 (11) , e3793. 10.1371/journal.pone.0003793

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Abstract

BackgroundIncreasing evidence suggests that individual isoforms of protein kinase C (PKC) play distinct roles in regulating platelet activation.Methodology/Principal FindingsIn this study, we focus on the role of two novel PKC isoforms, PKCδ and PKCε, in both mouse and human platelets. PKCδ is robustly expressed in human platelets and undergoes transient tyrosine phosphorylation upon stimulation by thrombin or the collagen receptor, GPVI, which becomes sustained in the presence of the pan-PKC inhibitor, Ro 31-8220. In mouse platelets, however, PKCδ undergoes sustained tyrosine phosphorylation upon activation. In contrast the related isoform, PKCε, is expressed at high levels in mouse but not human platelets. There is a marked inhibition in aggregation and dense granule secretion to low concentrations of GPVI agonists in mouse platelets lacking PKCε in contrast to a minor inhibition in response to G protein-coupled receptor agonists. This reduction is mediated by inhibition of tyrosine phosphorylation of the FcRγ-chain and downstream proteins, an effect also observed in wild-type mouse platelets in the presence of a PKC inhibitor.ConclusionsThese results demonstrate a reciprocal relationship in levels of the novel PKC isoforms δ and ε in human and mouse platelets and a selective role for PKCε in signalling through GPVI.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Publisher: Public Library of Science
ISSN: 1932-6203
Date of First Compliant Deposit: 13 January 2021
Date of Acceptance: 5 November 2008
Last Modified: 13 Jan 2021 14:30
URI: http://orca.cardiff.ac.uk/id/eprint/137525

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