Activation of protein kinase C (PKC) in platelets results in immediate phosphorylation of pleckstrin (previously called 40K or P47), the major PKC substrate in platelets. Pleckstrin contains a Ca2+-binding ‘EF-hand’ structure and PKC phosphorylation sites at Ser-113 and Ser-117. The N and C termini of pleckstrin contain two pleckstrin homology domains (PH), which mediate protein-protein and protein-lipid interactions. Pleckstrin is highly expressed in human neutrophils. Pleckstrin is rapidly phosphorylated following treatment of neutrophils in response to inflammatory stimuli, probably by nonconventional PKC isoforms delta or zeta, which are expressed in human neutrophils. Phosphorylation by nonconventional PKC isoforms induces a conformational change in pleckstrin that promotes its interaction with membranes and/or with the cytoskeleton, serving to target proteins or lipids recognized by PH domains to sites where they can contribute to the microbicidal response.
