Differential Roles of the PKC Novel Isoforms, PKCδ and PKCε, in Mouse and Human PlateletsReportar como inadecuado




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Background

Increasing evidence suggests that individual isoforms of protein kinase C PKC play distinct roles in regulating platelet activation.

Methodology-Principal Findings

In 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.

Conclusions

These 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.



Autor: Catherine J. Pears , Kelly Thornber , Jocelyn M. Auger, Craig E. Hughes, Beata Grygielska, Majd B. Protty, Andrew C. Pearce, Stev

Fuente: http://plos.srce.hr/



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