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Proline isomerases at the crossroads of protein folding, signal transduction, and immunosuppression.

Publication ,  Journal Article
Heitman, J; Movva, NR; Hall, MN
Published in: New Biol
May 1992

The immunosuppressants cyclosporin A (CsA), FK506, and rapamycin block T-cell activation by interfering with signal transduction. The institution of CsA therapy for prophylaxis against graft rejection revolutionized human organ transplants, and clinical trials with FK506 and rapamycin are in progress. The targets for these drugs, cyclophilin for CsA and FKBP for FK506 and rapamycin, are members of two unrelated families of ubiquitous, highly conserved, abundant proteins. Although unrelated, both cyclophilin and FKBP catalyze proline isomerization and may fold proteins. The structures of both cyclophilin and FKBP have been determined, in some cases in complex with drugs or substrates. The cyclophilin-CsA and FKBP-FK506 complexes prevent T-cell response to antigen, bind and modulate the activity of the protein phosphatase calcineurin, and prevent nuclear import of a subunit of NF-AT, a T-cell activation transcription factor. In contrast, rapamycin blocks T-cell responses to IL-2. Yeast genetic studies suggest that the FKBP-rapamycin target is a protein complex involved in cell cycle progression. Further studies should provide fundamental insights into T-cell activation, signal transduction, and protein folding, and hold the promise of more specific immunosuppressive therapies.

Duke Scholars

Published In

New Biol

ISSN

1043-4674

Publication Date

May 1992

Volume

4

Issue

5

Start / End Page

448 / 460

Location

United States

Related Subject Headings

  • Tacrolimus Binding Proteins
  • T-Lymphocytes
  • Signal Transduction
  • Saccharomyces cerevisiae
  • Protein Conformation
  • Peptidylprolyl Isomerase
  • Models, Molecular
  • Lymphocyte Activation
  • Immunosuppressive Agents
  • Humans
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Heitman, J., Movva, N. R., & Hall, M. N. (1992). Proline isomerases at the crossroads of protein folding, signal transduction, and immunosuppression. New Biol, 4(5), 448–460.
Heitman, J., N. R. Movva, and M. N. Hall. “Proline isomerases at the crossroads of protein folding, signal transduction, and immunosuppression.New Biol 4, no. 5 (May 1992): 448–60.
Heitman, J., et al. “Proline isomerases at the crossroads of protein folding, signal transduction, and immunosuppression.New Biol, vol. 4, no. 5, May 1992, pp. 448–60.

Published In

New Biol

ISSN

1043-4674

Publication Date

May 1992

Volume

4

Issue

5

Start / End Page

448 / 460

Location

United States

Related Subject Headings

  • Tacrolimus Binding Proteins
  • T-Lymphocytes
  • Signal Transduction
  • Saccharomyces cerevisiae
  • Protein Conformation
  • Peptidylprolyl Isomerase
  • Models, Molecular
  • Lymphocyte Activation
  • Immunosuppressive Agents
  • Humans