Isoform-specific functions of protein kinase C: the platelet paradigm.

Platelets are central to haemostasis and thrombosis. Many key steps in platelet activation and aggregation are regulated by members of the PKC (protein kinase C) family. Multiple isoforms of PKC are expressed in platelets, and evidence is emerging that different isoforms play distinct roles in the platelet activation process. This may, in part, be regulated by isoform-specific interactions between PKC family members and other intracellular signalling molecules, such as tyrosine kinases, or the actin cytoskeleton regulator, VASP (vasodilator-stimulated phosphoprotein). The contributions of individual PKC isoforms can be addressed directly in platelets from knockout mouse models, which are providing key insights into the physiological function of PKC isoform diversity and can be a valuable complimentary approach to more commonly used pharmacological analyses. Using knockout mouse models, recent reports have demonstrated the importance of PKCbeta and PKCtheta in integrin-dependent platelet spreading, and also a novel role for PKCdelta in regulating filopodial formation, highlighting the utility of such models to investigate the functions of specific PKC isoforms in a physiological process that is significant to our understanding of cardiovascular disease.