TNF ACTIVATES NF-KAPPA-B BY PHOSPHATIDYLCHOLINE-SPECIFIC PHOSPHOLIPASE-C-INDUCED ACIDIC SPHINGOMYELIN BREAKDOWN

被引：1053

作者：

SCHUTZE, S ^{[1
]}

POTTHOFF, K ^{[1
]}

MACHLEIDT, T ^{[1
]}

BERKOVIC, D ^{[1
]}

WIEGMANN, K ^{[1
]}

KRONKE, M ^{[1
]}

机构：

[1] UNIV GOTTINGEN, ZENTRUM INNERE MED, HAMATOL ONKOL ABT, W-3400 GOTTINGEN, GERMANY

来源：

CELL | 1992年 / 71卷 / 05期

关键词：

D O I：

10.1016/0092-8674(92)90553-O

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 [生物化学与分子生物学]; 081704 [应用化学];

摘要：

In this paper, we describe a phospholipid transmission pathway mediating tumor necrosis factor (TNF) activation of the nuclear transcription factor kappaB (NF-kappaB). Central to this TNF signaling route is the second messenger-like molecule ceramide, which is generated by sphingomyelin (SM) breakdown catalyzed by a sphingomyelinase (SMase). SMase activation is secondary to the generation of 1,2-diacylglycerol (DAG) produced by a TNF-responsive PC-specific phospholipase C (PC-PLC). The functional coupling of these two C type phospholipases is revealed by D609, a selective inhibitor of PC-PLC. SMase itself, or SMase-inducing regimens such as exogenous PLC or synthetic DAGs, induces NF-kappaB activation at pH 5.0, suggesting the operation of an acidic SMase. A model is proposed in which a TNF-responsive PC-PLC via DAG couples to an acidic SMase, resulting in the generation of ceramide, which eventually triggers rapid induction of nuclear NF-kappaB activity.

引用

页码：765 / 776

页数：12

共 72 条

[1]

A PROTEIN KINASE-C PSEUDOSUBSTRATE PEPTIDE INHIBITS PHOSPHORYLATION OF THE CD3 ANTIGEN IN STREPTOLYSIN-O-PERMEABILIZED HUMAN LYMPHOCYTES-T [J].

ALEXANDER, DR ;

HEXHAM, JM ;

LUCAS, SC ;

GRAVES, JD ;

CANTRELL, DA ;

CRUMPTON, MJ .

BIOCHEMICAL JOURNAL, 1989, 260 (03) :893-901

[2]

ATKINSON YH, 1990, IMMUNOLOGY, V70, P82

[3]

ACTIVATION OF DNA-BINDING ACTIVITY IN AN APPARENTLY CYTOPLASMIC PRECURSOR OF THE NF-KAPPA-B TRANSCRIPTION FACTOR [J].

BAEUERLE, PA ;

BALTIMORE, D .

CELL, 1988, 53 (02) :211-217

[4]

THE INDUCIBLE TRANSCRIPTION ACTIVATOR NF-KAPPA-B - REGULATION BY DISTINCT PROTEIN SUBUNITS [J].

BAEUERLE, PA .

BIOCHIMICA ET BIOPHYSICA ACTA, 1991, 1072 (01) :63-80

[5]

A 65-KD SUBUNIT OF ACTIVE NF-KAPPA-B IS REQUIRED FOR INHIBITION OF NF-KAPPA-B BY I-KAPPA-B [J].

BAEUERLE, PA ;

BALTIMORE, D .

GENES & DEVELOPMENT, 1989, 3 (11) :1689-1698

[6]

I-KAPPA-B - A SPECIFIC INHIBITOR OF THE NF-KAPPA-B TRANSCRIPTION FACTOR [J].

BAEUERLE, PA ;

BALTIMORE, D .

SCIENCE, 1988, 242 (4878) :540-546

[7]

THE V-REL ONCOGENE ENCODES A KAPPA-B ENHANCER BINDING-PROTEIN THAT INHIBITS NF-KAPPA-B FUNCTION [J].

BALLARD, DW ;

WALKER, WH ;

DOERRE, S ;

SISTA, P ;

MOLITOR, JA ;

DIXON, EP ;

PEFFER, NJ ;

HANNINK, M ;

GREENE, WC .

CELL, 1990, 63 (04) :803-814

[8]

TUMOR NECROSIS, CACHEXIA, SHOCK, AND INFLAMMATION - A COMMON MEDIATOR [J].

BEUTLER, B ;

CERAMI, A .

ANNUAL REVIEW OF BIOCHEMISTRY, 1988, 57 :505-518

[9]

NF-KAPPA-B AND RELATED PROTEINS - REL DORSAL HOMOLOGIES MEET ANKYRIN-LIKE REPEATS [J].

BLANK, V ;

KOURILSKY, P ;

ISRAEL, A .

TRENDS IN BIOCHEMICAL SCIENCES, 1992, 17 (04) :135-140

[10]

BLIGH EG, 1959, CAN J BIOCHEM PHYS, V37, P911

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