Pleckstrin homology domains and phospholipid-induced cytoskeletal reorganization

Abstract

At the moment of hemostasis, the platelet must be able to reorganize its cytoskeleton through a complexly orchestrated signaling cascade that is regulated, in part, by polyphosphoinositides. In the past 6 years, evidence has accumulated that PH domains bind these polyphosphoinositides and play a role in cytoskeletal changes. Work to date implies that the amino-terminal PH domain of pleckstrin induces a shift of F-actin towards the cell cortex and participates in the production of lamellipodia. The effect of pleckstrin on actin is, in turn, regulated by the phosphorylation of pleckstrin by PKC. Evidence also suggests that PH domains of Dbl family exchange factors play a role in the PI3K-stimulated activation of Rac. It is likely that the PH domains of pleckstrin, as well as the PH domains of the Dbl family of exchange factors, are only a few examples of PH domains that are able to influence the organization of the cytoskeleton.