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Calcium signalling in T cells stimulated by a cyclophilin B-binding protein

Nature volume 371, pages 355–358 (1994)Cite this article

Abstract

THE immunosuppressant drug cyclosporin A blocks a calcium-dependent signal from the T-cell receptor (TCR) that normally leads to T-cell activation1–3. When bound to cyclophilin, cyclosporin A binds and inactivates the key signalling intermediate calcineurin4–6. To identify potential cellular homologues of cyclosporin A that might regulate calcium signalling, we have cloned human genes encoding cyclophilin B-binding-proteins using the yeast two-hybrid system7,8. One gene product, when overexpressed in Jurkat T cells, specifically induced transcription from the inter-leukin-2 enhancer, by activating the T-cell-specific transcription factors NF-AT and NF-IL2A. This protein, termed calcium-signal modulating cyclophilin ligand (CAML), acts downstream of the TCR and upstream of calcineurin by causing an influx of calcium. CAML appears to be a new participant in the calcium-signal trans-duction pathway, implicating cyclophilin B in calcium signalling, even in the absence of cyclosporin.

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Authors and Affiliations

  1. Departments of Experimental Oncology and Hematology/Oncology, St Jude Children's Research Hospital, 332 N. Lauderdale, and Department of Pediatrics, University of Tennessee, Memphis, Tennessee, 38105, USA

    Richard J. Bram

  2. Howard Hughes Medical Institute and Department of Pathology, Stanford University, Stanford, California, 94305, USA

    Gerald R. Crabtreet

Authors
  1. Richard J. Bram
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  2. Gerald R. Crabtreet
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Bram, R., Crabtreet, G. Calcium signalling in T cells stimulated by a cyclophilin B-binding protein. Nature 371, 355–358 (1994). https://doi.org/10.1038/371355a0

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