P-selectin (CD62, GMP-140, PADGEM) belongs to the selectin family of adhesion molecules. P-selectin acts as a receptor that supports binding of leukocytes to activated platelets and endothelium. P-selectin-mediated adhesive interactions operate in conjunction with cell-cell interactions directed by related molecules and are likely to be important in both hemostatic and inflammatory processes. P-selectin is located in membranes of a granules in unstimulated platelets and redistributed to the cell surface upon platelet activation. P-selectin is also present in endothelial cells in membranes of Weibel-Palade bodies and megakaryocytes. Surface appearance of P-selectin is very rapid, but transient declining to basal level within short time following stimulation. P-selectin is a 140 kDa protein that is highly glycosylated. The cDNA-derived amino acid sequence predicts a molecule with a series of cysteine-rich domains. Like the other selectins P-selectin contains an N-terminal Ca2+ dependent lectin-like domain and an EGF-like motif which is followed by nine consensus repeats, a transmembrane domain, and a short cytoplasmic tail. The human gene for P-selectin is located on chromosome 1q21–24. P-selectin is a receptor for neutrophils and monocytes, recognizing oligosaccharide structures on the target cells. The physiologic role of P-selectin might be the mediation of initial leukocyte adhesion to activated endothelium during acute inflammation. It may work in concert with E-selectin to direct early, regionally specific adherence of neutrophils and monocytes at sites of acute inflammation. A soluble form of P-selectin found in serum and plasma has been described which might represent a proteolytic fragment or more likely a soluble splice variant lacking the transmembrane domain. Soluble P-selectin is a potentially important molecule to provide more detailed insight into pathological situations. Excessive accumulation of neutrophils on the endothelial surface accompanied by high exposure of P-selectin has been implicated in a number of inflammatory disorders, including adult respiratory distress syndrome, acute lung injury, ischemiareperfusion injury, Gram-negative septic shock, thrombotic diseases and rheumatoid arthritis. Malignant cells were shown to express receptors for P-selectin suggesting an important role for P-selectin in tumor formation and metastasis. Platelets have also been shown to promote tumor metastasis.
- References to P-Selectin (Granule membrane protein 140, PADGEM, CD62P)