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

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...

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Bibliographic Details
Published in:	Nature (London) Vol. 371; no. 6495; pp. 355 - 358
Main Authors:	Bram, Richard J, Crabtreet, Gerald R
Format:	Journal Article
Language:	English
Published:	London Nature Publishing 22-09-1994 Nature Publishing Group
Subjects:	Adaptor Proteins, Signal Transducing Amino Acid Isomerases - metabolism Amino Acid Sequence Base Sequence Biological and medical sciences Calcium Calcium - metabolism calcium-signal modulating cyclophilin ligand protein CAML protein Carrier Proteins - genetics Carrier Proteins - metabolism Cell Line Cell physiology Cellular biology Cloning, Molecular cyclophilin B-binding protein Cyclophilins Cyclosporine - pharmacology DNA DNA-Binding Proteins - metabolism Fundamental and applied biological sciences. Psychology gene regulation Genes Humans Lymphocyte Activation lymphocytes T man Molecular and cellular biology Molecular Sequence Data Mutation NFATC Transcription Factors Nuclear Proteins Peptidylprolyl Isomerase Protein Kinase C - metabolism Proteins RNA, Messenger - metabolism Signal Transduction T-Lymphocytes - drug effects T-Lymphocytes - immunology T-Lymphocytes - metabolism Tacrolimus - pharmacology transcription Transcription Factors - metabolism Transcription, Genetic Transfection Yeast Yeasts Human Binding protein Signal transduction Peptidylprolyl isomerase Isomerases Calcium Enzyme T-Lymphocyte Immunosuppressive agent Mechanism of action cis-trans-Isomerases
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Summary:	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.
Bibliography:	ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 ObjectType-Article-1 ObjectType-Feature-2
ISSN:	0028-0836 1476-4687
DOI:	10.1038/371355a0