LAT palmitoylation: Its essential role in membrane microdomain targeting and tyrosine phosphorylation during T cell activation

被引:746
作者
Zhang, WG [1 ]
Trible, RP [1 ]
Samelson, LE [1 ]
机构
[1] National Institute Child Health & Human Dev, Cell Biol & Metab Branch, Sect Lymphocyte Signaling, NIH, Bethesda, MD 20892 USA
关键词
D O I
10.1016/S1074-7613(00)80606-8
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
The linker molecule LAT is a critical substrate of the tyrosine kinases activated upon TCR engagement. Phosphorylated LAT binds Grb2, PLC-gamma 1, and other signaling molecules. We demonstrate that human LAT is palmitoylated and that palmitoylated LAT predominantly localizes into glycolipid-enriched microdomains (GEMs). Although the LAT transmembrane domain is sufficient for membrane localization, palmitoylation at C26 and C29 is essential for efficient partitioning into GEMs. LAT palmitoylation is necessary for its tyrosine phosphorylation. After T cell activation, most tyrosine-phosphorylated LAT molecules and a fraction of PLC-gamma 1 and other signaling molecules are present in GEMs. LAT is central to T cell activation and is a novel linker molecule shown to require targeting to membrane microdomains for signaling.
引用
收藏
页码:239 / 246
页数:8
相关论文
共 39 条
  • [11] FC-EPSILON-RI-MEDIATED RECRUITMENT OF P53/56(LYN) TO DETERGENT-RESISTANT MEMBRANE DOMAINS ACCOMPANIES CELLULAR SIGNALING
    FIELD, KA
    HOLOWKA, D
    BAIRD, B
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1995, 92 (20) : 9201 - 9205
  • [12] Compartmentalized activation of the high affinity immunoglobulin E receptor within membrane domains
    Field, KA
    Holowka, D
    Baird, B
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 1997, 272 (07) : 4276 - 4280
  • [13] Caveolae, DIGs, and the dynamics of sphingolipid-cholesterol microdomains
    Harder, T
    Simons, K
    [J]. CURRENT OPINION IN CELL BIOLOGY, 1997, 9 (04) : 534 - 542
  • [14] S-acylation of LCK protein tyrosine kinase is essential for its signalling function in T lymphocytes
    Kabouridis, PS
    Magee, AI
    Ley, SC
    [J]. EMBO JOURNAL, 1997, 16 (16) : 4983 - 4998
  • [15] The role of Grb2-associated proteins in T-cell activation
    Koretzky, GA
    [J]. IMMUNOLOGY TODAY, 1997, 18 (08): : 401 - 406
  • [16] MONOCLONAL ANTIBODIES DEFINING DISTINCTIVE HUMAN T-CELL SURFACE-ANTIGENS
    KUNG, PC
    GOLDSTEIN, G
    REINHERZ, EL
    SCHLOSSMAN, SF
    [J]. SCIENCE, 1979, 206 (4416) : 347 - 349
  • [17] EVIDENCE FOR A REGULATED INTERACTION BETWEEN HETEROTRIMERIC G-PROTEINS AND CAVEOLIN
    LI, SW
    OKAMOTO, T
    CHUN, MY
    SARGIACOMO, M
    CASANOVA, JE
    HANSEN, SH
    NISHIMOTO, I
    LISANTI, MP
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 1995, 270 (26) : 15693 - 15701
  • [18] LUBLIN DM, 1992, CURR TOP MICROBIOL, V178, P141
  • [19] MARTH JD, 1989, J IMMUNOL, V142, P2430
  • [20] PROTEIN MODULES AND SIGNALING NETWORKS
    PAWSON, T
    [J]. NATURE, 1995, 373 (6515) : 573 - 580