Abstract
P-selectin binding to neutrophils requires a specific protein, P-selectin glycoprotein ligand 1 (PSGL-1), as well as sialyl-Lewis X (sLex) glycan determinants. We have found that a short segment near the amino terminus of PSGL-1 that contains a tyrosine sulfation consensus is essential for P-selectin adhesion and that addition of the amino-terminal segment to some but not all mucin-like molecules confers on those molecules the ability to bind P-selectin. PSGL-1 synthesized in the presence of sulfation inhibitors binds P-selectin weakly, and within the amino-terminal 20 residues, mutation of the tyrosines to phenylalanine abolishes binding. Rolling of HL-60 cells on P-selectin-coated coverslips is strongly attenuated by treatment of cells with an inhibitor of sulfation.
Publication types
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Comparative Study
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Sequence
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Animals
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Cell Adhesion / physiology
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Cells, Cultured
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Chlorates / pharmacology
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Consensus Sequence
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DNA Mutational Analysis
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Endothelium, Vascular / physiology
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HL-60 Cells
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Humans
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Leukocytes / physiology
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Ligands
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Membrane Glycoproteins / genetics
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Membrane Glycoproteins / metabolism*
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Molecular Sequence Data
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Mucins / genetics
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Mucins / metabolism*
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Oligosaccharides
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P-Selectin / metabolism*
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Peptide Fragments / metabolism
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Protein Binding
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Protein Processing, Post-Translational* / drug effects
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Recombinant Fusion Proteins / metabolism
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Sequence Deletion
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Sialyl Lewis X Antigen
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Transfection
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Tyrosine / analogs & derivatives*
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Tyrosine / biosynthesis
Substances
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Chlorates
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Ligands
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Membrane Glycoproteins
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Mucins
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Oligosaccharides
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P-Selectin
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P-selectin ligand protein
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Peptide Fragments
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Recombinant Fusion Proteins
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Sialyl Lewis X Antigen
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tyrosine O-sulfate
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Tyrosine