Genetic evidence for Shc requirement in TCR-induced c-Rel nuclear translocation and IL-2 expression

被引:28
|
作者
Iwashima, M
Takamatsu, M
Yamagishi, H
Hatanaka, Y
Huang, YY
McGinty, C
Yamasaki, S
Koike, T
机构
[1] Med Coll Georgia, Inst Mol Med & Genet, Augusta, GA 30912 USA
[2] Mitsubishi Kagaku Inst Life Sci, Machida, Tokyo 1948511, Japan
[3] Chiba Univ, Sch Med, Dept Mol Genet, Chiba 2608670, Japan
关键词
D O I
10.1073/pnas.082647499
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
She, a prototypic adapter molecule, has been implicated in T cell receptor (TCR) signal transduction, but its role has not been identified clearly. Here we report that She is essential for TCR-induced IL-2 production but is dispensable for CD69 or CD25 expression. Engagement of TCR in mutant Jurkat T cells lacking She fails to produce IL-2 because of impaired mitogen-activated protein kinase activation. Activation of c-Rel, a transcription factor essential for IL-2 expression, was impaired also. In contrast, activation of nuclear factor of activated T cell and expression of CD69/CD25 were comparable between the mutant and wild-type Jurkat cells. These defects were rescued by expression of exogenous She. Activation of c-Rel using the estrogen receptor fusion protein restored the activation of the IL-2 promoter in an estrogen-dependent manner. These results show that She plays an essential role in the TCR-induced activation of c-Rel and the IL-2 promoter.
引用
收藏
页码:4544 / 4549
页数:6
相关论文
共 47 条
  • [1] Essential role for IKKγ/NEMO in TCR-induced IL-2 expression in Jurkat T cells
    He, KL
    Ting, AT
    EUROPEAN JOURNAL OF IMMUNOLOGY, 2003, 33 (07) : 1917 - 1924
  • [2] c-Rel is required for chromatin remodeling across the IL-2 gene promoter
    Rao, S
    Gerondakis, S
    Woltring, D
    Shannon, MF
    JOURNAL OF IMMUNOLOGY, 2003, 170 (07): : 3724 - 3731
  • [3] c-Rel regulation of IL-2 gene expression may be mediated through activation of AP-1
    Shapiro, VS
    Mollenauer, MN
    Greene, WC
    Weiss, A
    JOURNAL OF EXPERIMENTAL MEDICINE, 1996, 184 (05): : 1663 - 1669
  • [4] FUNCTIONAL INVOLVEMENT OF C-REL IN THE ACTIVATION OF THE IL-2 PROMOTER BY CD28 COSTIMULATION
    TAN, TH
    RICE, N
    BRYAN, R
    RICH, R
    LI, YQ
    HORVATH, G
    LAI, JH
    JOURNAL OF CELLULAR BIOCHEMISTRY, 1994, : 434 - 434
  • [5] Interferon regulatory factor-4 activates IL-2 and IL-4 promoters in cooperation with c-Rel
    Shindo, Hisakazu
    Yasui, Kiyoshi
    Yamamoto, Kazuo
    Honma, Kiri
    Yui, Katsuyuki
    Kohno, Tomoko
    Ma, Yuhua
    Chua, Koon Jiew
    Kubo, Yoshinao
    Aihara, Hitoshi
    Ito, Takashi
    Nagayasu, Takeshi
    Matsuyama, Toshifumi
    Hayashi, Hideki
    CYTOKINE, 2011, 56 (03) : 564 - 572
  • [6] GB Virus C Envelope Protein E2 Inhibits TCR-Induced IL-2 Production and Alters IL-2-Signaling Pathways
    Bhattarai, Nirjal
    McLinden, James H.
    Xiang, Jinhua
    Kaufman, Thomas M.
    Stapleton, Jack T.
    JOURNAL OF IMMUNOLOGY, 2012, 189 (05): : 2211 - 2216
  • [7] IL-2 SIGNAL TRANSDUCTION - IL-2 INDUCED TRANSLOCATION OF PROTEIN-KINASE-C
    GIRI, JG
    GROSS, JL
    ENDERS, LD
    DEXTER, DL
    ROBB, RJ
    PROCEEDINGS OF THE AMERICAN ASSOCIATION FOR CANCER RESEARCH, 1987, 28 : 338 - 338
  • [8] Smad3 is essential for TGF-β1 to suppress IL-2 production and TCR-induced proliferation, but not IL-2-induced proliferation
    McKarns, SC
    Schwartz, RH
    Kaminski, NE
    JOURNAL OF IMMUNOLOGY, 2004, 172 (07): : 4275 - 4284
  • [9] Cutting edge: TCR-induced NAB2 enhances T cell function by coactivating IL-2 transcription
    Collins, Samuel
    Wolfraim, Lawrence A.
    Drake, Charles G.
    Horton, Maureen R.
    Powell, Jonathan D.
    JOURNAL OF IMMUNOLOGY, 2006, 177 (12): : 8301 - 8305
  • [10] Gα12 is critical for TCR-induced IL-2 production and differentiation of T helper 2 and T helper 17 cells
    Won, Hee Yeon
    Min, Hyun Jung
    Lee, Woo Hyung
    Kim, Sang Geon
    Hwang, Eun Sook
    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2010, 394 (03) : 811 - 816