       Document 0416
 DOCN  M9640416
 TI    TNF-induced activation of NF-kappa B.
 DT    9604
 AU    Schutze S; Wiegmann K; Machleidt T; Kronke M; Institut fur Medizinische
       Mikrobiologie und Hygiene, Technische; Universitat Munchen, Germany.
 SO    Immunobiology. 1995 Jul;193(2-4):193-203. Unique Identifier : AIDSLINE
       MED/96030040
 AB    Tumor Necrosis Factor (TNF) is one of the most potent physiological
       inducers of the nuclear transcription factor NF-kappa B. In light of the
       pivotal role of NF-kappa B in the development of immune responses and
       activation of HIV replication, the identification of TNF signal
       transduction pathways involved in NF-kappa B activation is of particular
       interest. Data from our laboratory demonstrate that the TNF signal
       transduction pathway-mediating NF-kappa B activation involves two
       phospholipases, a phosphatidylcholine-specific phospholipase C (PC-PLC)
       and an endosomal acidic sphingomyelinase (aSMase). The aSMase activation
       by TNF is secondary to the generation of 1,2-diacylglycerol (DAG)
       produced by a TNF-responsive PC-PLC. SMase and its product ceramide
       induce degradation of the NF-kappa B inhibitor I kappa B as well as
       NF-kappa B activation. Besides endosomal acidic SMase, TNF also rapidly
       activates a plasmamembrane-associated neural SMase (nSMase), that,
       however is not involved in TNF-induced NF-kappa B activation. NSMase and
       aSMase are activated by different cytoplasmic domains of the 55 kDa
       TNF-receptor and are coupled to select pathways of TNF signaling.
       Ceramide generated by nSMase directs the activation of proline-directed
       serin/threonine protein kinases and phospholipase A2 and ceramide
       produced by aSMase triggers the activation of NF-kappa B. No apparent
       crosstalk was detected between nSMase and aSMase pathways, indicating
       that ceramide action depends on the topology of its production.
 DE    Amino Acid Sequence  Animal  Human  Molecular Sequence Data  NF-kappa
       B/*BIOSYNTHESIS/DRUG EFFECTS  Signal Transduction/DRUG
       EFFECTS/*IMMUNOLOGY  Support, Non-U.S. Gov't  Tumor Necrosis
       Factor/*PHYSIOLOGY  JOURNAL ARTICLE  REVIEW  REVIEW, TUTORIAL

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).

