title: Tyrosine sulphation of sphingosine 1-phosphate 1 (S1P1) is required for S1P-mediated cell migration in primary cultures of human umbilical vein endothelial cells.
abstract: Sphingosine 1-phosphate (S1P), a lysophospholipid mediator, regulates diverse functions of many types of cells by binding to specific G protein-coupled receptors termed S1P(1)-S1P(5). In T-cells, tyrosine sulphation of S1P(1) is required for high-affinity binding of S1P and fully functional signalling. In this study, we showed that tyrosine sulphation of S1P(1) is necessary for S1P-induced Src phosphorylation and migration in human umbilical vein endothelial cells (HUVECs). Both substitution of phenylalanine (F) for tyrosine (Y) in S1P(1) and inhibition of tyrosine sulphation blocked c-Src phosphorylation and migration in HUVECs. In addition, overexpression of mutant (F19, 22F) S1P(1), lacking tyrosine sulphation sites, suppressed native S1P(1) effects on migration, actin rearrangement and lamellipodia formation. Therefore, tyrosine sulphation of S1P(1) is required for its optimal transduction of signals from S1P in HUVECs.
authors.affiliation: Department of Life Science, College of Medicine, National Taiwan University, Taipei, Taiwan, ROC.
authors.forename: Yuan-Li
authors.initials: YL
authors.lastname: Huang
authors.forename: Hsiao-Sheng
authors.initials: HS
authors.lastname: Lin
authors.forename: Shee-Uan
authors.initials: SU
authors.lastname: Chen
authors.forename: Hsinyu
authors.initials: H
authors.lastname: Lee
mesh_terms: D000595:Amino Acid Sequence; D015153:Blotting, Western; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism*; D005434:Flow Cytometry; D006801:Humans; D008246:Lysophospholipids / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology*; D008969:Molecular Sequence Data; D009154:Mutation; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D013455:Sulfur / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism*; D014471:Umbilical Veins / Q000166:cytology
chemical_list: D008246:Lysophospholipids; D011994:Recombinant Proteins; C060506:sphingosine 1-phosphate; D014443:Tyrosine; D013455:Sulfur; D013110:Sphingosine