Cutting edge: Tyrosine-independent transmission of inhibitory signals by CTLA-4

被引:40
作者
Cinek, T
Sadra, A
Imboden, JB
机构
[1] Univ Calif San Francisco, San Francisco, CA 94143 USA
[2] San Francisco Gen Hosp, Dept Med, Rosaland Russell Res Lab, San Francisco, CA 94143 USA
关键词
D O I
10.4049/jimmunol.164.1.5
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
CTLA-4 is an important inhibitor of T cell activation, We used Jurkat cells expressing mutants of murine CTLA-4 to study the structural requirements for inhibitory signaling. We find that signals for the inhibition of IL-2 secretion are delivered efficiently by a CTLA-4 mutant in which both cytoplasmic tyrosines have been replaced by phenylalanines. A CTLA-4 mutant that larks the carboxyl-terminal half of the intracellular domain also retains the ability to inhibit, but deletion of an additional 11 aa completely abrogates that capability. We conclude that delivery of an inhibitory signal requires the membrane-proximal region of the CTLA-1 cytoplasmic domain and does not depend upon the tyrosine phosphorylation of CTLA-4.
引用
收藏
页码:5 / 8
页数:4
相关论文
共 21 条
[1]   Interaction of the cytoplasmic tail of CTLA-4 (CD152) with a clathrin-associated protein is negatively regulated by tyrosine phosphorylation [J].
Bradshaw, JD ;
Lu, P ;
Leytze, G ;
Rodgers, J ;
Schieven, GL ;
Bennett, KL ;
Linsley, PS ;
Kurtz, SE .
BIOCHEMISTRY, 1997, 36 (50) :15975-15982
[2]   Cytotoxic T lymphocyte antigen 4 (CTLA-4) interferes with extracellular signal-regulated kinase (ERK) and Jun NH4-terminal kinase (JNK) activation, but does not affect phosphorylation of T cell receptor zeta and ZAP70 [J].
Calvo, CR ;
Amsen, D ;
Kruisbeek, AM .
JOURNAL OF EXPERIMENTAL MEDICINE, 1997, 186 (10) :1645-1653
[3]  
Chuang E, 1999, J IMMUNOL, V162, P1270
[4]  
Chuang E, 1997, J IMMUNOL, V159, P144
[5]  
Fraser JH, 1999, EUR J IMMUNOL, V29, P838
[6]   Two distinct regions of the CD28 intracytoplasmic domain are involved in the tyrosine phosphorylation of Vav and GTPase activating protein-associated p62 protein [J].
Klasen, S ;
Pages, F ;
Peyron, JF ;
Cantrell, DA ;
Olive, D .
INTERNATIONAL IMMUNOLOGY, 1998, 10 (04) :481-489
[7]   Molecular basis of T cell inactivation by CTLA-4 [J].
Lee, KM ;
Chuang, E ;
Griffin, M ;
Khattri, R ;
Hong, DK ;
Zhang, WG ;
Straus, D ;
Samelson, LE ;
Thompson, CB ;
Bluestone, JA .
SCIENCE, 1998, 282 (5397) :2263-2266
[8]   CYTOTOXIC T-LYMPHOCYTE-ASSOCIATED MOLECULE-4, A HIGH AVIDITY RECEPTOR FOR CD80 AND CD86, CONTAINS AN INTRACELLULAR-LOCALIZATION MOTIF IN ITS CYTOPLASMIC TAIL [J].
LEUNG, HT ;
BRADSHAW, J ;
CLEAVELAND, JS ;
LINSLEY, PS .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1995, 270 (42) :25107-25114
[9]   Intracellular trafficking of CTLA-4 and focal localization towards sites of TCR engagement [J].
Linsley, PS ;
Bradshaw, J ;
Greene, J ;
Peach, R ;
Bennett, KL ;
Mittler, RS .
IMMUNITY, 1996, 4 (06) :535-543
[10]   Regulation of T cell receptor signaling by tyrosine phosphatase SYP association with CTLA-4 [J].
Marengere, LEM ;
Waterhouse, P ;
Duncan, GS ;
Mittrucker, HW ;
Feng, GS ;
Mak, TW .
SCIENCE, 1996, 272 (5265) :1170-1173