PMID- 7608202
OWN - NLM
STAT- MEDLINE
DCOM- 19950816
LR  - 20210210
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 270
IP  - 27
DP  - 1995 Jul 7
TI  - Fc epsilon RI-mediated induction of nuclear factor of activated T-cells.
PG  - 16333-8
AB  - Nuclear factor of activated T-cells (NFAT) is a transcriptional activator that 
      binds to the interleukin-2 promoter and is believed to be responsible for 
      T-cell-specific interleukin-2 gene expression. Here we demonstrate using 
      electrophoretic mobility shift assays that nuclear NFAT can be induced in the rat 
      basophilic leukemia (RBL-2H3) mast cell line and rat bone marrow-derived mast 
      cells upon cross-linkage of the high affinity receptor (Fc epsilon RI) for 
      immunoglobulin E (IgE). Receptor-dependent activation of NFAT was mimicked by the 
      combination of the protein kinase C activator phorbol myristate acetate and the 
      calcium ionophore ionomycin. The induced binding activity was specific for the 
      NFAT recognition motif because competition with nonradioactive NFAT 
      oligonucleotide abolished the DNA binding activity, whereas nonradioactive 
      oligonucleotides recognized by the transcription factors NF kappa B, 
      glucocorticoid receptors, and TFIID did not. An oligonucleotide representing the 
      AP-1 recognition sequence also blocked the NFAT DNA binding activity, as did a 
      combination of anti-Fos and anti-Jun antibodies. Using electrophoretic mobility 
      shift assays, AP-1-binding proteins were found to be induced in RBL-2H3 cells 
      under the same conditions as was the NFAT binding activity. Together these data 
      suggest that the NFAT complex in mast cells contains Fos and Jun proteins as does 
      NFAT in T-cells. The appearance of nuclear NFAT binding activity was dependent in 
      part upon calcium mobilization, as buffering the antigen-induced calcium rise 
      with intracellular BAPTA strongly inhibited NFAT activation. Prevention of 
      calcium influx with external EGTA also inhibited NFAT activation, indicating that 
      release of calcium from internal stores was insufficient for sustained activation 
      of mast cell NFAT. Cyclosporin A, a potent inhibitor of the calmodulin-dependent 
      phosphatase calcineurin, blocked the induction of NFAT-DNA binding activity, 
      implicating calcineurin as a key signaling enzyme in this pathway. These results 
      suggest that NFAT is present in the mast cell line RBL-2H3 and in primary bone 
      marrow-derived mast cells, is similar in subunit composition to the T-cell NFAT, 
      and may play a role in calcium-dependent signal transduction in mast cells.
FAU - Hutchinson, L E
AU  - Hutchinson LE
AD  - Department of Zoology and Genetics, Iowa State University, Ames 50011, USA.
FAU - McCloskey, M A
AU  - McCloskey MA
LA  - eng
GR  - GM48144/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Cross-Linking Reagents)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (NFATC Transcription Factors)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Receptors, IgE)
RN  - 0 (Transcription Factor AP-1)
RN  - 0 (Transcription Factors)
RN  - 83HN0GTJ6D (Cyclosporine)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Animals
MH  - Base Sequence
MH  - Bone Marrow Cells
MH  - Calcium/pharmacology
MH  - Cells, Cultured
MH  - Cross-Linking Reagents
MH  - Cyclosporine/pharmacology
MH  - DNA-Binding Proteins/*biosynthesis/metabolism
MH  - *Gene Expression Regulation
MH  - Kinetics
MH  - Leukemia, Basophilic, Acute
MH  - Mast Cells/*metabolism
MH  - Molecular Sequence Data
MH  - NFATC Transcription Factors
MH  - *Nuclear Proteins
MH  - Protein Binding
MH  - Rats
MH  - Receptors, IgE/*metabolism
MH  - *Signal Transduction/drug effects
MH  - Transcription Factor AP-1/biosynthesis
MH  - Transcription Factors/*biosynthesis/metabolism
EDAT- 1995/07/07 00:00
MHDA- 1995/07/07 00:01
CRDT- 1995/07/07 00:00
PHST- 1995/07/07 00:00 [pubmed]
PHST- 1995/07/07 00:01 [medline]
PHST- 1995/07/07 00:00 [entrez]
AID - S0021-9258(17)48867-3 [pii]
AID - 10.1074/jbc.270.27.16333 [doi]
PST - ppublish
SO  - J Biol Chem. 1995 Jul 7;270(27):16333-8. doi: 10.1074/jbc.270.27.16333.