title: Tyrosine sulfation of P-selectin glycoprotein ligand-1 is required for high affinity binding to P-selectin.
abstract: P-selectin glycoprotein ligand-1 (PSGL-1) is a mucin-like glycoprotein on leukocytes that is a high affinity ligand for P-selectin. Previous studies have shown that sialylation and fucosylation of PSGL-1 are required for its binding to P-selectin, but other post-translational modifications of PSGL-1 may also be important. We demonstrate that PSGL-1 synthesized in human HL-60 cells can be metabolically labeled with [35S]sulfate that is incorporated primarily into tyrosine sulfate. Treatment of PSGL-1 with a bacterial arylsulfatase releases sulfate from tyrosine, resulting in a concordant decrease in binding to P-selectin. These studies demonstrate that tyrosine sulfate on PSGL-1 functions in conjunction with sialylated and fucosylated glycans to mediate high affinity binding to P-selectin.
authors.affiliation: Departments of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City 73190, USA.
authors.forename: P P
authors.initials: PP
authors.lastname: Wilkins
authors.forename: K L
authors.initials: KL
authors.lastname: Moore
authors.forename: R P
authors.initials: RP
authors.lastname: McEver
authors.forename: R D
authors.initials: RD
authors.lastname: Cummings
mesh_terms: D001192:Arylsulfatases / Q000378:metabolism; D001345:Autoradiography; D004591:Electrophoresis, Polyacrylamide Gel; D018922:HL-60 Cells; D006801:Humans; D007700:Kinetics; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000302:isolation & purification / Q000378:metabolism*; D019007:P-Selectin / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D013431:Sulfates / Q000378:metabolism*; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000032:analysis / Q000378:metabolism
chemical_list: D008562:Membrane Glycoproteins; D019007:P-Selectin; C084882:P-selectin ligand protein; D013431:Sulfates; C005662:tyrosine O-sulfate; D014443:Tyrosine; D001192:Arylsulfatases