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

Richard J Bram, Gerald R. Crabtree

Research output: Contribution to journalArticle

131 Citations (Scopus)

Abstract

The immunosuppressant drug cyclosporin A blocks a calcium-dependent signal from the T-cell receptor (TCR) that normally leads to T-cell activation. When bound to cyclophilin, cyclosporin A binds and inactivates the key signalling intermediate calcineurin. 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 system. One gene product, when overexpressed in Jurkat T cells, specifically induced transcription from the interleukin-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 transduction pathway, implicating cyclophilin B in calcium signalling, even in the absence of cyclosporin.

Original languageEnglish (US)
Pages (from-to)355-358
Number of pages4
JournalNature
Volume371
Issue number6495
DOIs
StatePublished - Sep 22 1994
Externally publishedYes

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Calcium Signaling
Carrier Proteins
Cyclophilins
Cyclosporine
Calcium
T-Lymphocytes
Calcineurin
T-Cell Antigen Receptor
NFATC Transcription Factors
Ligands
Two-Hybrid System Techniques
Jurkat Cells
Immunosuppressive Agents
Genes
Interleukin-2
Signal Transduction
cyclophilin B
Pharmaceutical Preparations
Proteins

ASJC Scopus subject areas

  • General

Cite this

Calcium signalling in T cells stimulated by a cyclophilin B-binding protein. / Bram, Richard J; Crabtree, Gerald R.

In: Nature, Vol. 371, No. 6495, 22.09.1994, p. 355-358.

Research output: Contribution to journalArticle

Bram, Richard J ; Crabtree, Gerald R. / Calcium signalling in T cells stimulated by a cyclophilin B-binding protein. In: Nature. 1994 ; Vol. 371, No. 6495. pp. 355-358.
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