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 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.
Mesh Terms:
Adaptor Proteins, Signal Transducing, Amino Acid Isomerases, Amino Acid Sequence, Base Sequence, Calcium, Carrier Proteins, Cell Line, Cloning, Molecular, Cyclophilins, Cyclosporine, DNA, DNA-Binding Proteins, Humans, Lymphocyte Activation, Molecular Sequence Data, Mutation, NFATC Transcription Factors, Nuclear Proteins, Peptidylprolyl Isomerase, Protein Kinase C, RNA, Messenger, Signal Transduction, T-Lymphocytes, Tacrolimus, Transcription Factors, Transcription, Genetic, Transfection
Nature
Date: Sep. 22, 1994
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