Molecular mechanisms of immunosuppression by cyclosporine, FK506, and rapamycin
作者:
Maria Cardenas,
Dahai Zhu,
Joseph Heitman,
期刊:
Current Opinion in Nephrology and Hypertension
(OVID Available online 1995)
卷期:
Volume 4,
issue 6
页码: 472-477
ISSN:1062-4821
年代: 1995
出版商: OVID
数据来源: OVID
摘要:
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.
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