L-selectin binds to P-selectin glycoprotein ligand-1 on leukocytes: interactions between the lectin, epidermal growth factor, and consensus repeat domains of the selectins determine ligand binding specificity.
The selectins mediate cellular interactions by binding carbohydrate determinants present on a limited number of glycoprotein ligands. L-selectin binds multiple ligands expressed on endothelial cells, while P-selectin interacts exclusively with P-selectin glycoprotein ligand-1 (PSGL-1) on leukocytes. In this study, L-selectin was shown to bind leukocytes through the P-selectin ligand, PSGL-1, although at lower levels than P-selectin. L-selectin binding to PSGL-1 is specific since it was blocked by Abs to L-selectin or PSGL-1, required appropriate glycosylation of PSGL-1, and was Ca2+ dependent. The contributions of the extracellular domains of the selectins to ligand binding was assessed using a panel of chimeric selectins created by exchange of domains between L-selectin and P- or E-selectin. The lectin and epidermal growth factor domains of L- and P-selectin contributed significantly to binding through similar, if not identical, regions of PSGL-1. The different chimeric selectins revealed that the lectin domain was the dominant determinant for ligand binding, while cooperative interactions between the lectin, epidermal growth factor, and short consensus repeat domains of the selectins also modified ligand binding specificity. L-selectin binding to PSGL-1 expressed by leukocytes may mediate neutrophil rolling on stationary leukocytes bound to cytokine-induced endothelial cells, which was previously reported to be a L-selectin-dependent process.
Department of Immunology, Duke University Medical Center, Durham, NC 27710, USA.
L
L
Tu
A
A
Chen
M D
MD
Delahunty
K L
KL
Moore
S R
SR
Watson
R P
RP
McEver
T F
TF
Tedder
D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D016384:Consensus Sequence; D018076:DNA, Complementary / Q000235:genetics; D004730:Endothelium, Vascular / Q000378:metabolism; D004815:Epidermal Growth Factor / Q000378:metabolism*; D006031:Glycosylation; D018922:HL-60 Cells / Q000378:metabolism; D006801:Humans; D019041:L-Selectin / Q000378:metabolism*; D007962:Leukocytes / Q000378:metabolism*; D046911:Macromolecular Substances; D008562:Membrane Glycoproteins / Q000378:metabolism*; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000378:metabolism; D011485:Protein Binding; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012091:Repetitive Sequences, Nucleic Acid; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid
D018076:DNA, Complementary; D046911:Macromolecular Substances; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; C084882:P-selectin ligand protein; D011993:Recombinant Fusion Proteins; D019041:L-Selectin; D004815:Epidermal Growth Factor