Pleckstrin

Pleckstrin is a cytoskeletal protein originally identified in platelets and leukocytes. It is a substrate for protein kinase C (PKC) when cells are activated and plays a role in cytoskeletal reorganization during activation events. In humans, the pleckstrin protein is encoded by the PLEK gene and is most abundant in hematopoietic cells.

The term pleckstrin homology (PH) domain, a common structural motif in signaling proteins, derives from pleckstrin. The PH domain is about 100-120 amino acids long and binds phosphoinositides such as phosphatidylinositol-4,5-bisphosphate (PIP2), recruiting proteins to membranes and coordinating signaling cascades. Pleckstrin participates in interactions with the actin cytoskeleton and membrane-associated complexes.

Functional studies indicate that upon activation, pleckstrin becomes phosphorylated on serine residues, contributing to changes in platelet shape and spreading. It also associates with cytoskeletal elements and has been used as a marker for PKC activity in hematopoietic cells. The protein's precise roles may vary with cell type and activation state.

Pleckstrin-related research informs understanding of platelet biology and signal transduction in immune cells. While not a dominant signaling hub on its own, its discovery helped identify the PH domain family, which now encompasses many signaling proteins involved in membrane targeting and lipid signaling.