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PSGL-1 binding to selectins is regulated by a series of glycosyltransferases and sulfotransferases required to make it a functional selectin ligand.

STEPHEN FOSTER MD FACS, FACR, in Managing the Allergic Patient, 2008 Selectin Antagonist: sPSGL-1 P-selectin glycoprotein ligand-1 (PSGL-1) is expressed on the surface of most leukocytes and is a counter-receptor for P-selectin.

It has been shown to bind E- and L-selectin, 123 transmembrane adhesion receptors that mediate the initial rolling interaction between leukocytes and the vascular endothelium prior to extravasation.

A soluble, extracellular form of human PSGL-1 (sPSGL-1) has been shown to bind all members of the selectin family.

This shows promise in disrupting the inflammatory cycle by impeding leukocyte adhesion and diapedesis.

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View chapter Purchase book Read full chapter URL: Leukocyte Migration and Adhesion Beat A.

Imhof, Dominique Dunon, in Advances in Immunology, 1995 C P-SELECTIN LIGANDS Two P-selectin ligands have been characterized so far: the recently cloned molecule P-selectin glycoprotein ligand-1 (PSGL-1) ( Fig.

Da ligand (103105).

Surprisingly, L-selectin might also be a ligand for P-selectin and E-selectin (106): first, because the rolling of leukocytes on a platelet layer could be inhibited by antibodies directed against P-selectin or E-selectin (106,107); and second, since L-selectin can bear sialylated carbohydrates which serve as ligands for P-selectin and E-selectin.

PSGL-1 Recently, PSGL-1, a P-selectin ligand, was isolated by screening for transfected cDNA that translated ligand activity (103).

The screening was performed with COS cells cotransfected with 34-fucosyl- transferase which allowed the correct glycosylation of the protein necessary for P-selectin recognition.

It was a 120-kDa (reduced form, 250-kDa nonreduced) sialoprotein and its binding to P-selectin affinity columns was Ca 2 dependent (104).

The ligand contained the sLex motif, and -2-3 linked sialic acids which are most probably O-linked (105).

However, the amount of sLex contained in the 120-kDa ligand was less than 1 of the total cell membrane-bound sLex.

The 120-kDa protein may serve as a specific selectin ligand because the sugar side chains form a clustered patch of sialylated fucosylated O-linked oligosaccharides (105).

Albeit likely, the similarity of this protein to PSGL-1 awaits further clarification.

View chapter Purchase book Read full chapter URL: Najalysin Herbert J.

Evans, in Handbook of Proteolytic Enzymes (Third Edition), 2013 Activity and Specificity Treatment of PSGL-1 with N.

The enzyme also cleaves the -chain of the platelet glycoprotein GPIbVIX complex at Glu282Asp283.

The common features of these two specificities are the Asp residue at P and the presence of three potentially sulfated Tyr residues in a negative cluster on the N-terminal side of the scissile bond 9.

The first cleavage occurs at about residue 520 of the 610 in the A chain, or about 90 residues from the C-terminus of the chain.

The C-terminal 10 kDa peptide is released, whereas the remainder of the chain is held by disulfides to the rest of the molecule.

Prolonged treatment of fibrinogen results in cleavage at other sites farther from the C-terminus of the A-chain, releasing one or more additional peptides.

Fibrinogen treated with najalysin remains clottable by thrombin ( Chapter 643 ), indicating that the N-terminal region of the molecule is unaffected 11.

The fibrinogen A-chain contains very few Tyr residues in the region of cleavage, suggesting the specificity may differ from that of N.

Both najalysins can be assayed based on their effects on their specific substrates, either by SDS-PAGE analysis of cleavage, or loss of their biological effect.

An assay based on the inactivation of 2 -macroglobulin can also be used 13.

View chapter Purchase book Read full chapter URL: The Microcirculation in Inflammation Klaus Ley, in Microcirculation, 2008 9.8.5 PSGL-1 (CD162) The most important selectin ligand on leukocytes is P-selectin glycoprotein ligand-1 (PSGL-1, CD162).

PSGL-1 is a misnomer, because PSGL-1 also binds L- and E-selectins with similar affinity as P-selectin 307.

Almost all leukocytes express PSGL-1 protein on the cell surface, but not all cell surface-expressed PSGL-1 can bind selectins.