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PMID: 7532676 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

FK506 inhibits antigen receptor-mediated induction of c-rel in B and T lymphoid cells.

The Journal of experimental medicine ·Vol. 181 ·No. 3 ·1995-03-01 ·Pages 1091-9

Venkataraman L, Burakoff SJ, Sen R

Abstract

Stimulation of B and T cells via the antigen receptor, by phorbol ester or by phorbol ester and ionomycin, leads to nuclear translocation of the inducible transcription factor NF-kappa B, comprising the p50 and p65 rel-related polypeptides. In this report we show that c-rel is a component of the antigen receptor-induced kappa B binding proteins in both B and T cells. Whereas NF-kappa B can be induced by phorbol ester alone, optimal induction of c-rel requires stimulation by both phorbol ester and ionomycin, the dual signal that is necessary for proliferation of untransformed lymphocytes. Furthermore, c-rel induction is blocked by the immunosuppressive drug FK506 that is known to inhibit B and T cell activation. c-rel-dependent transactivation of the interleukin-2 receptor alpha chain (IL-2R alpha) promoter is augmented by coexpression of calcineurin, suggesting the involvement of a calcineurin-dependent intracellular pathway. Our results identify c-rel as a target of immunosuppressive agents and illustrate the similarity of activation pathways in both B and T cells.

MeSH Terms
Amino Acid Sequence Animals B-Lymphocytes/metabolism Calcineurin Calmodulin-Binding Proteins/analysis,physiology Ionomycin/pharmacology Mice Molecular Sequence Data NF-kappa B/metabolism Phosphoprotein Phosphatases/analysis,physiology Polyenes/pharmacology Proto-Oncogene Proteins/biosynthesis Proto-Oncogene Proteins c-rel Receptors, Antigen, B-Cell/physiology Receptors, Antigen, T-Cell/physiology Receptors, Interleukin-1/genetics Sirolimus T-Lymphocytes/metabolism Tacrolimus/pharmacology Tetradecanoylphorbol Acetate/pharmacology Tumor Cells, Cultured
Chemicals
Calmodulin-Binding Proteins NF-kappa B Polyenes Proto-Oncogene Proteins Proto-Oncogene Proteins c-rel Receptors, Antigen, B-Cell Receptors, Antigen, T-Cell Receptors, Interleukin-1 Ionomycin Calcineurin Phosphoprotein Phosphatases Tetradecanoylphorbol Acetate Sirolimus Tacrolimus
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Venkataraman L
Rosenstiel Research Center, Brandeis University, Waltham, Massachusetts 02254-9110.
Burakoff S J
Sen R
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38 references, click to expand
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Article Info
Journal
The Journal of experimental medicine
Abbr.
J Exp Med
ISSN
0022-1007
DOI
10.1084/jem.181.3.1091
Published
1995-03-01
Pages
1091-9
Language
English
Region
United States
NLM ID
2985109R
PMCID
PMC2191924
Subset
IM
External Links
PubMed source DOI: 10.1084/jem.181.3.1091 PMC Full Text View journal details
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