Molecular mechanisms of immunosuppression by cyclosporine, FK506, and rapamycin.
Journal Article (Journal Article;Review)
The immunosuppressant cyclosporine A revolutionized treatment of graft rejection. Two newer agents, FK506 and rapamycin, show great clinical potential. These drugs suppress the immune system by forming protein-drug complexes that interact with and inhibit key components of the signal transduction pathways required for T-cell activation. The target of the cyclophilin A-cyclosporine A and FKBP12-FK506 complexes is calcineurin, a protein phosphatase required for signaling via the T-cell receptor. Cyclosporine A and FK506 nephrotoxicity may reflect renal-specific functions of calcineurin. The target of the FKBP12-rapamycin complex is TOR, a lipid and protein kinase homolog that is likely to be required for T-cell proliferation in response to interleukin-2. The identification of cyclosporine A, FK506, and rapamycin targets reveals much concerning T-cell signaling and provides the means to design novel immunosuppressants with reduced toxicity.
Full Text
Duke Authors
Cited Authors
- Cardenas, ME; Zhu, D; Heitman, J
Published Date
- November 1995
Published In
Volume / Issue
- 4 / 6
Start / End Page
- 472 - 477
PubMed ID
- 8591053
International Standard Serial Number (ISSN)
- 1062-4821
Digital Object Identifier (DOI)
- 10.1097/00041552-199511000-00002
Language
- eng
Conference Location
- England