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

Nature. 1994 Sep 22;371(6495):355-8. doi: 10.1038/371355a0.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adaptor Proteins, Signal Transducing*
  • Amino Acid Isomerases / metabolism*
  • Amino Acid Sequence
  • Base Sequence
  • Calcium / metabolism*
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Cell Line
  • Cloning, Molecular
  • Cyclophilins*
  • Cyclosporine / pharmacology
  • DNA
  • DNA-Binding Proteins / metabolism
  • Humans
  • Lymphocyte Activation
  • Molecular Sequence Data
  • Mutation
  • NFATC Transcription Factors
  • Nuclear Proteins*
  • Peptidylprolyl Isomerase
  • Protein Kinase C / metabolism
  • RNA, Messenger / metabolism
  • Signal Transduction*
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism*
  • Tacrolimus / pharmacology
  • Transcription Factors / metabolism
  • Transcription, Genetic
  • Transfection


  • Adaptor Proteins, Signal Transducing
  • CAMLG protein, human
  • Carrier Proteins
  • DNA-Binding Proteins
  • NFATC Transcription Factors
  • Nuclear Proteins
  • RNA, Messenger
  • Transcription Factors
  • cyclophilin B
  • Cyclosporine
  • DNA
  • Protein Kinase C
  • Amino Acid Isomerases
  • Cyclophilins
  • Peptidylprolyl Isomerase
  • Calcium
  • Tacrolimus

Associated data

  • GENBANK/U18242