NF-ATp, a T lymphocyte DNA-binding protein that is a target for calcineurin and immunosuppressive drugs.

作者: P.G. McCaffrey , B.A. Perrino , T.R. Soderling , A. Rao

DOI: 10.1016/S0021-9258(18)53757-1

关键词:

摘要: The nuclear factor of activated T cells (NF-AT) is essential for transcription the interleukin-2 gene upon cell activation. Here we use a technique involving elution and renaturation proteins from SDS-acrylamide gels to identify DNA-binding component NF-AT (NF-ATp) that present in hypotonic extracts prior activation appears when are activated. NF-ATp resting predominantly form migrating with an apparent molecular weight 110,000-140,000, while migrates lower (90,000-125,000). This difference likely reflect dephosphorylation NF-ATp, since treatment calf intestinal phosphatase or calcium- calmodulin-dependent calcineurin vitro results similar decrease its weight. We show dephosphorylated lysates by calcium-dependent process blocked inclusion EGTA specific peptide inhibitor lysis buffer. Moreover, inhibited immunosuppressive drugs cyclosporin A FK506, which inhibit activity complexed their binding proteins, cyclophilin FK506-binding protein. work identifies as phosphoprotein target drug/immunophilin/calcineurin complexes thought mediate inhibition induction FK506.

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