Blocked signal transduction to the ERK and JNK protein kinases in anergic CD4(+) T cells

被引：406
作者：
Li, W
Whaley, CD
Mondino, A
Mueller, DL
机构：
[1] UNIV MINNESOTA, SCH MED, DEPT MED, MINNEAPOLIS, MN 55455 USA
[2] UNIV MINNESOTA, SCH MED, DEPT MICROBIOL, MINNEAPOLIS, MN 55455 USA
[3] UNIV MINNESOTA, SCH MED, CTR IMMUNOL, MINNEAPOLIS, MN 55455 USA
来源：
SCIENCE | 1996年 / 271卷 / 5253期
关键词：
D O I：
10.1126/science.271.5253.1272
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：
T cells activated by antigen receptor stimulation in the absence of accessory cell-derived costimulatory signals lose the capacity to synthesize the growth factor interleukin-2 (IL-2), a state called clonal anergy. An analysis of CD3- and CD28-induced signal transduction revealed reduced ERK and JNK enzyme activities in murine anergic T cells. The amounts of ERK and JNK proteins were unchanged, and the kinases could be fully activated in the presence of phorbol 12-myristrate 13-acetate. Dephosphorylation of the calcineurin substrate NFATp (preexisting nuclear factor of activated T cells) also remained inducible. These results suggest that a specific block in the activation of ERK and JNK contributes to defective IL-2 production in clonal anergy.
引用
收藏
页码：1272 / 1276
页数：5
相关论文
共 49 条
[1]   A THEORY OF SELF-NONSELF DISCRIMINATION [J].
BRETSCHER, P ;
COHN, M .
SCIENCE, 1970, 169 (3950) :1042-+
[2]  
CHAO TSO, 1992, J BIOL CHEM, V267, P19876
[3]  
CHO EA, 1993, J IMMUNOL, V151, P20
[4]   THE SMALL GTP-BINDING PROTEINS RAC1 AND CDC42 REGULATE THE ACTIVITY OF THE JNK/SAPK SIGNALING PATHWAY [J].
COSO, OA ;
CHIARIELLO, M ;
YU, JC ;
TERAMOTO, H ;
CRESPO, P ;
XU, NG ;
MIKI, T ;
GUTKIND, JS .
CELL, 1995, 81 (07) :1137-1146
[5]   THE PRIMARY STRUCTURE OF MEK, A PROTEIN-KINASE THAT PHOSPHORYLATES THE ERK GENE-PRODUCT [J].
CREWS, CM ;
ALESSANDRINI, A ;
ERIKSON, RL .
SCIENCE, 1992, 258 (5081) :478-480
[6]   ACTIVATION OF MITOGEN-ACTIVATED PROTEIN-KINASE KINASE BY V-RAF IN NIH 3T3 CELLS AND INVITRO [J].
DENT, P ;
HASER, W ;
HAYSTEAD, TAJ ;
VINCENT, LA ;
ROBERTS, TM ;
STURGILL, TW .
SCIENCE, 1992, 257 (5075) :1404-1407
[7]   JNK1 - A PROTEIN-KINASE STIMULATED BY UV-LIGHT AND HA-RAS THAT BINDS AND PHOSPHORYLATES THE C-JUN ACTIVATION DOMAIN [J].
DERIJARD, B ;
HIBI, M ;
WU, IH ;
BARRETT, T ;
SU, B ;
DENG, TL ;
KARIN, M ;
DAVIS, RJ .
CELL, 1994, 76 (06) :1025-1037
[8]   STIMULATION OF P21RAS UPON T-CELL ACTIVATION [J].
DOWNWARD, J ;
GRAVES, JD ;
WARNE, PH ;
RAYTER, S ;
CANTRELL, DA .
NATURE, 1990, 346 (6286) :719-723
[9]   SINGLE CELL ASSAY OF A TRANSCRIPTION FACTOR REVEALS A THRESHOLD IN TRANSCRIPTION ACTIVATED BY SIGNALS EMANATING FROM THE T-CELL ANTIGEN RECEPTOR [J].
FIERING, S ;
NORTHROP, JP ;
NOLAN, GP ;
MATTILA, PS ;
CRABTREE, GR ;
HERZENBERG, LA .
GENES & DEVELOPMENT, 1990, 4 (10) :1823-1834
[10]   CLONING OF B7-2 - A CTLA-4 COUNTER-RECEPTOR THAT COSTIMULATES HUMAN T-CELL PROLIFERATION [J].
FREEMAN, GJ ;
GRIBBEN, JG ;
BOUSSIOTIS, VA ;
NG, JW ;
RESTIVO, VA ;
LOMBARD, LA ;
GRAY, GS ;
NADLER, LM .
SCIENCE, 1993, 262 (5135) :909-911
12345