A novel, high endothelial venule-specific sulfotransferase expresses 6-sulfo sialyl Lewis(x), an L-selectin ligand displayed by CD34.
L-selectin mediates lymphocyte homing by facilitating lymphocyte adhesion to unique carbohydrate ligands, sulfated sialyl Lewis(x), which are expressed on high endothelial venules (HEV) in secondary lymphoid organs. The nature of the sulfotransferase(s) that contribute to sulfation of such L-selectin counterreceptors has been uncertain. We herein describe a novel L-selectin ligand sulfotransferase, termed LSST, that directs the synthesis of the 6-sulfo sialyl Lewis(x) on L-selectin counterreceptors CD34, GlyCAM-1, and MAdCAM-1. LSST is predominantly expressed in HEV and exhibits striking catalytic preference for core 2-branched mucin-type O-glycans as found in natural L-selectin counterreceptors. LSST enhances L-selectin-mediated adhesion under shear compared to nonsulfated controls. LSST therefore corresponds to an HEV-specific sulfotransferase that contributes to the biosynthesis of L-selectin ligands required for lymphocyte homing.
Hiraoka
N
N
Glycobiology Program, Cancer Research Center, The Burnham Institute, La Jolla, California 92037, USA.
Petryniak
B
B
Nakayama
J
J
Tsuboi
S
S
Suzuki
M
M
Yeh
J C
JC
Izawa
D
D
Tanaka
T
T
Miyasaka
M
M
Lowe
J B
JB
Fukuda
M
M
D000117:Acetylglucosamine / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism*; D001483:Base Sequence; D016466:CHO Cells; D002236:Carbohydrate Conformation; D002240:Carbohydrate Sequence; D006224:Cricetinae; D018076:DNA, Complementary / Q000302:isolation & purification; D004729:Endothelium, Lymphatic / Q000201:enzymology* / Q000276:immunology* / Q000378:metabolism; D005647:Fucosyltransferases / Q000096:biosynthesis / Q000378:metabolism; D006801:Humans; D006965:Hyperplasia; D019041:L-Selectin / Q000378:metabolism* / Q000502:physiology; D016256:Lewis X Antigen / Q000031:analogs & derivatives; D008024:Ligands; D051379:Mice; D008806:Mice, Inbred AKR; D008969:Molecular Sequence Data; D009077:Mucins / Q000378:metabolism; D009844:Oligosaccharides / Q000096:biosynthesis* / Q000276:immunology / Q000378:metabolism; D012212:Rheology; D000080506:Sialyl Lewis X Antigen / Q000031:analogs & derivatives; D013431:Sulfates / Q000378:metabolism; D015238:Sulfotransferases / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D013950:Thymus Gland / Q000201:enzymology / Q000378:metabolism / Q000473:pathology
C086949:6'-sulfated sialyl Lewis x; D018952:Antigens, CD34; D018076:DNA, Complementary; D016256:Lewis X Antigen; D008024:Ligands; D009077:Mucins; D009844:Oligosaccharides; D000080506:Sialyl Lewis X Antigen; D013431:Sulfates; D019041:L-Selectin; D005647:Fucosyltransferases; C031692:galactoside 3-fucosyltransferase; C120484:HEV-specific LSST; D015238:Sulfotransferases; D000117:Acetylglucosamine