Protein Kinase Cδ Differentially Regulates Platelet Functional Responses

Objective-Protein Kinase C delta (PKC delta) is expressed in platelets and activated downstream of protease-activated receptors (PAR)s and glycoprotein VI (GPVI) receptors. The purpose of this study was to investigate the role of PKC delta in platelets. Methods and Results-We evaluated the role of PKC delta in platelets using two approaches-pharmacological and molecular genetic approach. In human platelets pretreated with isoform selective antagonistic RACK peptide (delta V1-1)TAT, and in the murine platelets lacking PKC delta, PAR4-mediated dense granule secretion was inhibited, whereas GPVI-mediated dense granule secretion was potentiated. These effects were statistically significant in the absence and presence of thromboxane A(2)(TXA(2)). Furthermore, TXA(2) generation was differentially regulated by PKC delta. However, PKC delta had a small effect on platelet P-selectin expression. Calcium- and PKC-dependent pathways independently activate fibrinogen receptor in platelets. When calcium pathways are blocked by dimethyl-BAPTA, AYPGKF-induced aggregation in PKC delta null mouse platelets and in human platelets pretreated with (delta V1-1)TAT, was inhibited. In a FeCl3-induced injury in vivo thrombosis model, PKC delta(-/-) mice occluded similar to their wild-type littermates. Conclusions-Hence, we conclude that PKC delta differentially regulates platelet functional responses such as dense granule secretion and TXA(2) generation downstream of PARs and GPVI receptors, but PKC delta deficiency does not affect the thrombus formation in vivo. (Arterioscler Thromb Vasc Biol. 2009; 29: 699-705.)