S1P1-selective in vivo-active agonists from high-throughput screening:: Off-the-shelf chemical probes of receptor interactions, signaling, and fate

被引:214
作者
Jo, EJ
Sanna, G
Gonzalez-Cabrera, PJ
Thangada, S
Tigyi, G
Osborne, DA
Hla, T
Parrill, AL
Rosen, H
机构
[1] Scripps Res Inst, Dept Immunol, La Jolla, CA 92037 USA
[2] Univ Connecticut, Hlth Ctr, Dept Cell Biol, Ctr Vasc Biol, Farmington, CT 06030 USA
[3] Univ Tennessee, Ctr Hlth Sci, Dept Cell Biol, Memphis, TN 38163 USA
[4] Univ Tennessee, Ctr Hlth Sci, Dept Physiol, Memphis, TN 38163 USA
[5] Univ Memphis, Dept Chem, Memphis, TN 38152 USA
来源
CHEMISTRY & BIOLOGY | 2005年 / 12卷 / 06期
关键词
D O I
10.1016/j.chembiol.2005.04.019
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The essential role of the sphingosine 1-phosphate (S1P) receptor S1P, in regulating lymphocyte trafficking was demonstrated with the S1P(1)-selective nanomolar agonist, SEW2871. Despite its lack of charged headgroup, the tetraaromatic compound SEW2871 binds and activates S1P(1) through a combination of hydrophobic and ion-dipole interactions. Both S1P and SEW2871 activated ERK, Akt, and Rac signaling pathways and induced S1P1 internalization and recycling, unlike FTY720-phosphate, which induces receptor degradation. Agonism with receptor recycling is sufficient for alteration of lymphocyte trafficking by S1P and SEW2871. S1P1 modeling and mutagenesis studies revealed that residues binding the S1P headgroup are required for kinase activation by both S1P and SEW2871. Therefore, SEW2871 recapitulates the action of S1P in all the signaling pathways examined and overlaps in interactions with key headgroup binding receptor residues, presumably replacing salt-bridge interactions with ion-dipole interactions.
引用
收藏
页码:703 / 715
页数:13
相关论文
共 64 条
  • [1] Expression of the sphingosine 1-phosphate receptor, S1P1, on T-cells controls thymic emigration
    Allende, ML
    Dreier, JL
    Mandala, S
    Proia, RL
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2004, 279 (15) : 15396 - 15401
  • [2] Sphingosine 1-phosphate-induced cell proliferation, survival, and related signaling events mediated by G protein-coupled receptors Edg3 and Edg5
    An, SZ
    Zheng, YH
    Bleu, T
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2000, 275 (01) : 288 - 296
  • [3] Ballesteros JA, 1995, Methods Neurosci, V25, P366, DOI [DOI 10.1016/S1043-9471(05)80049-7, 10.1016/S1043-9471(05)80049-7]
  • [4] Dynamic modeling of EDG1 receptor structural changes induced by site-directed mutations
    Bautista, DL
    Baker, DL
    Wang, D
    Fischer, DJ
    Van Brocklyn, J
    Spiegel, S
    Tigyi, G
    Parrill, AL
    [J]. JOURNAL OF MOLECULAR STRUCTURE-THEOCHEM, 2000, 529 : 219 - 224
  • [5] The immune modulator FTY720 targets sphingosine 1-phosphate receptors
    Brinkmann, V
    Davis, MD
    Heise, CE
    Albert, R
    Cottens, S
    Hof, R
    Bruns, C
    Prieschl, E
    Baumruker, T
    Hiestand, P
    Foster, CA
    Zollinger, M
    Lynch, KR
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (24) : 21453 - 21457
  • [6] Candelore MR, 2002, BIOCHEM BIOPH RES CO, V297, P600
  • [7] Rac regulates endothelial morphogenesis and capillary assembly
    Connolly, JO
    Simpson, N
    Hewlett, L
    Hall, A
    [J]. MOLECULAR BIOLOGY OF THE CELL, 2002, 13 (07) : 2474 - 2485
  • [8] A 2ND GENERATION FORCE-FIELD FOR THE SIMULATION OF PROTEINS, NUCLEIC-ACIDS, AND ORGANIC-MOLECULES
    CORNELL, WD
    CIEPLAK, P
    BAYLY, CI
    GOULD, IR
    MERZ, KM
    FERGUSON, DM
    SPELLMEYER, DC
    FOX, T
    CALDWELL, JW
    KOLLMAN, PA
    [J]. JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1995, 117 (19) : 5179 - 5197
  • [9] Sphingosine 1-phosphate and control of vascular tone
    Dantas, APV
    Igarashi, J
    Michel, T
    [J]. AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY, 2003, 284 (06): : H2045 - H2052
  • [10] Sphingosine 1-phosphate triggers both apoptotic and survival signals for human hepatic myofibroblasts
    Davaille, J
    Li, LY
    Mallat, A
    Lotersztajn, S
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (40) : 37323 - 37330