Fas ligation induces apoptosis and Jun kinase activation independently of CD45 and Lck in human T cells

被引:120
作者
Latinis, KM
Koretzky, GA
机构
[1] UNIV IOWA,DEPT INTERNAL MED,IOWA CITY,IA 52242
[2] UNIV IOWA,DEPT IMMUNOL,IOWA CITY,IA 52242
关键词
D O I
10.1182/blood.V87.3.871.bloodjournal873871
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Stimulation through the Fas/APO-1 receptor results in apoptosis through an incompletely characterized signaling pathway. More is known regarding signal transduction events that occur after ligation of the T-cell antigen receptor (TCR). It has been shown that TCR stimulation requires both the membrane tyrosine phosphatase, CD45, and the Src-family kinase, Lck, to result in cellular activation, Although prior studies suggest a role for protein tyrosine kinases and phosphatases in Fas signaling, we report here that Fas ligation induces apoptosis in T cells deficient in either CD45 or Lck, Further, in normal and CD45- or Lck-deficient cell lines, Fas stimulation results in activation of Jun kinase (JNK), a proposed mediator of stress activation pathways. Previous studies have also demonstrated a role for endogenous ceramide release in Pas-mediated apoptosis. We show that stimulation with a synthetic ceramide analog results in JNK activation as well as apoptosis, suggesting ceramide release occurs proximal to JNK activation in Fas signaling, Our data suggest that although CD45 and Lck are not required for Fas signaling, JNK activation may play an important role transducing distal signals that lead to apoptosis after Fas ligation. (C) 1996 by The American Society of Hematology.
引用
收藏
页码:871 / 875
页数:5
相关论文
共 39 条
[1]   CRYSTAL-STRUCTURE OF THE SOLUBLE HUMAN 55 KD TNF RECEPTOR-HUMAN TNF-BETA COMPLEX - IMPLICATIONS FOR TNF RECEPTOR ACTIVATION [J].
BANNER, DW ;
DARCY, A ;
JANES, W ;
GENTZ, R ;
SCHOENFELD, HJ ;
BROGER, C ;
LOETSCHER, H ;
LESSLAUER, W .
CELL, 1993, 73 (03) :431-445
[2]   CD28 COSTIMULATION CAN PROMOTE T-CELL SURVIVAL BY ENHANCING THE EXPRESSION OF BCL-X(L) [J].
BOISE, LH ;
MINN, AJ ;
NOEL, PJ ;
JUNE, CH ;
ACCAVITTI, MA ;
LINDSTEN, T ;
THOMPSON, CB .
IMMUNITY, 1995, 3 (01) :87-98
[3]   ANISOMYCIN-ACTIVATED PROTEIN KINASE-P45 AND KINASE-P55 BUT NOT MITOGEN-ACTIVATED PROTEIN KINASE-ERK-1 AND KINASE-ERK-2 ARE IMPLICATED IN THE INDUCTION OF C-FOS AND C-JUN [J].
CANO, E ;
HAZZALIN, CA ;
MAHADEVAN, LC .
MOLECULAR AND CELLULAR BIOLOGY, 1994, 14 (11) :7352-7362
[4]   FADD, A NOVEL DEATH DOMAIN-CONTAINING PROTEIN, INTERACTS WITH THE DEATH DOMAIN OF FAS AND INITIATES APOPTOSIS [J].
CHINNAIYAN, AM ;
OROURKE, K ;
TEWARI, M ;
DIXIT, VM .
CELL, 1995, 81 (04) :505-512
[5]  
CIFONE MG, 1993, J EXP MED, V177, P1547
[6]  
EISCHEN CM, 1994, J IMMUNOL, V153, P1947
[7]   DOMINANT INTERFERING FAS GENE-MUTATIONS IMPAIR APOPTOSIS IN A HUMAN AUTOIMMUNE LYMPHOPROLIFERATIVE SYNDROME [J].
FISHER, GH ;
ROSENBERG, FJ ;
STRAUS, SE ;
DALE, JK ;
MIDDELTON, LA ;
LIN, AY ;
STROBER, W ;
LENARDO, MJ ;
PUCK, JM .
CELL, 1995, 81 (06) :935-946
[8]   AN OSMOSENSING SIGNAL-TRANSDUCTION PATHWAY IN MAMMALIAN-CELLS [J].
GALCHEVAGARGOVA, Z ;
DERIJARD, B ;
WU, IH ;
DAVIS, RJ .
SCIENCE, 1994, 265 (5173) :806-808
[9]  
GULBINS E, 1995, IMMUNITY, V2, P41
[10]  
HANNUN YA, 1994, J BIOL CHEM, V269, P3125