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August 1, 1993Molecular and Cellular BiologyOpen Access

Identification of the immunophilins capable of mediating inhibition of signal transduction by cyclosporin A and FK506: roles of calcineurin binding and cellular location.

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Authors

RBRichard J. BramDHDeborah T. HungPMPatrick K. Martin

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Overview

Randomized trial identifies immunophilins mediating signal transduction inhibition in T-cells, suggesting potential therapeutic implications.

Key Points

  • This research aims to determine which immunophilins mediate the inhibitory effects of cyclosporin A and FK506 on T-cell function.
  • Overexpression of cyclophilin A, B, and FKBP12 was performed to assess T-cell sensitivity to CsA and FK506.
  • In vitro experiments measured the Ki of each drug-immunophilin complex for calcineurin.
  • Gene deletions were utilized to evaluate the effects of altered intracellular localization of cyclophilins B and C.
  • Overexpression of cyclophilin A or B and FKBP12 enhanced T-cell sensitivity to CsA or FK506, respectively.
  • Cyclophilin C, FKBP13, and FKBP25 did not exhibit any inhibitory effects.
  • Alterations in subcellular localization of cyclophilins B and C significantly changed their activities.

Cite This Study

Bram et al. (1993) studied this question.

synapsesocial.com/papers/6a11090b6da82ae745f3369chttps://doi.org/10.1128/mcb.13.8.4760
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