Tyrosine sulphation of sphingosine 1-phosphate 1 (S1P1) is required for S1P-mediated cell migration in primary cultures of human umbilical vein endothelial cells.
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.
Huang
Yuan-Li
YL
Department of Life Science, College of Medicine, National Taiwan University, Taipei, Taiwan, ROC.
Lin
Hsiao-Sheng
HS
Chen
Shee-Uan
SU
Lee
Hsinyu
H
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
D008246:Lysophospholipids; D011994:Recombinant Proteins; C060506:sphingosine 1-phosphate; D014443:Tyrosine; D013455:Sulfur; D013110:Sphingosine