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 isciform-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 isciforms 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 PKC beta and PKC theta in integrin-dependent platelet spreading, and also a novel role for PKC delta in regulating filopodial formation, highlighting the utility of such models to investigate the functions of specific PKC isciforms in a physiological process that is significant to our understanding of cardiovascular disease.