       Document 0035
 DOCN  M9620035
 TI    Costimulation requirement for AP-1 and NF-kappa B transcription factor
       activation in T cells.
 DT    9602
 AU    Jung S; Yaron A; Alkalay I; Hatzubai A; Avraham A; Ben-Neriah Y;
       Lautenberg Center for General and Tumor Immunology, Hebrew; University,
       Hadassah Medical School, Jerusalem, Israel.
 SO    Ann N Y Acad Sci. 1995 Sep 7;766:245-52. Unique Identifier : AIDSLINE
       MED/96049646
 AB    The transcriptional activity of the IL-2 promoter requires T-cell
       costimulation delivered by the TCR and the auxiliary receptor CD28.
       Several transcription factors participate in IL-2 promoter activation,
       among which are AP-1-like factors and NF-kappa B. Protein
       phosphorylation has an important role in the regulation of these two
       factors: (1) it induces the transactivating capacity of the AP-1 protein
       c-Jun; and (2) it is involved in the release of the cytoplasmic
       inhibitor, I kappa B, from NF-kappa B, allowing translocation of the
       latter into the nucleus. We have recently shown that both
       phosphorylation processes require T-cell costimulation. Furthermore, in
       activated T cells, the kinetics of the two phosphorylation events are
       essentially similar. According to our results, however, the kinases
       responsible for the two processes are distinct entities. Whereas TPCK
       inhibits phosphorylation of I kappa B and, consequently, activation of
       NF-kappa B, it markedly enhances the activity of JNK, the MAP
       kinase-related kinase that phosphorylates the transactivation domain of
       c-Jun. We, therefore, propose the activation scheme presented in FIGURE
       3 for T-cell costimulation. Costimulation results in the activation of a
       signaling pathway that leads to the simultaneous induction of the two
       transcription factors, AP-1 and NF-kappa B. Integration of the signals
       generated by TCR and CD28 engagement occurs along this pathway, which
       then bifurcates to induce I kappa B phosphorylation and NF-kappa B
       activation on the one hand, and JNK activation and c-Jun phosphorylation
       on the other. We are currently engaged in defining where the two signals
       integrate along the AP-1/NF-kappa B pathway.
 DE    Antibodies/PHARMACOLOGY  Antigens, CD28/IMMUNOLOGY  Calmodulin-Dependent
       Protein Kinases/METABOLISM  Cell Line  Enzyme Activation  Human  *HIV
       Long Terminal Repeat  Interleukin-2/*BIOSYNTHESIS/GENETICS
       Luciferase/BIOSYNTHESIS  *Lymphocyte Transformation  Models, Biological
       Muromonab-CD3/PHARMACOLOGY  NF-kappa B/*METABOLISM  Phosphorylation
       Promoter Regions (Genetics)  Proto-Oncogene Proteins c-jun/METABOLISM
       Recombinant Proteins/BIOSYNTHESIS  T-Lymphocytes/*IMMUNOLOGY/*METABOLISM
       Tetradecanoylphorbol Acetate/PHARMACOLOGY  Transcription Factor
       AP-1/*METABOLISM  Transfection  Tumor Cells, Cultured  JOURNAL ARTICLE

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

