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

Lakshmi Venkataraman, Steven J. Burakoff, Ranjan Sen

Research output: Contribution to journalArticle

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-κB, comprising the p50 and p65 rel- related polypeptides. In this report we show that c-rel is a component of the antigen receptor-induced κB binding proteins in both B and T cells. Whereas NF-κB 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 α chain (IL-2Rα) 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.

Original languageEnglish (US)
Pages (from-to)1091-1099
Number of pages9
JournalJournal of Experimental Medicine
Volume181
Issue number3
DOIs
StatePublished - Mar 1 1995
Externally publishedYes

ASJC Scopus subject areas

  • Immunology

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