Calcium signalling in T cells stimulated by a cyclophilin B-binding protein
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.
- Publication:
-
Nature
- Pub Date:
- September 1994
- DOI:
- 10.1038/371355a0
- Bibcode:
- 1994Natur.371..355B