Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 1992;12(4):303-13.
doi: 10.3109/08916939209148473.

FK 506 and autoimmune disease: perspective and prospects

A W Thomson  1 , T E Starzl
Affiliations
Review

FK 506 and autoimmune disease: perspective and prospects

A W Thomson et al. Autoimmunity. 1992.
No abstract available

PubMed Disclaimer

Figures

Figure 1
Figure 1
Structures of the immunosuppressive macrolides FK 506 and Rapamycin showing the FKBP binding domain and the effector element of each molecule.
Figure 2
Figure 2
Within the T lymphocyte, FK 506-FKBP or CsA-cyclophilin complexes bind with high affinity to calcineurin-calmodulin to form a pentameric complex which interferes with Ca++-dependent signalling pathways. Complexes of RAPA-FKBP do not bind to calcineurin. Recent observations indicate that calcineurin (a protein phosphatase) is the target of the FK 506-FKBP and CsA-cyclophilin complexes. CaM=calmodulin; CNA=calcineurin A; CNB=calcineurin B; CYP=cyclophilin; FKBP=FK 506 binding protein.
Figure 3
Figure 3
Influence of FK 506 on signal transduction within T cells. The crucial event in T-cell activation stimulated by antigen plus IL-1 would appear to be activation of the phospholipase which splits phosphatidyl inositol diphosphate into the reactive products diacylglycerol and inositol triphosphate. The increased intracellular calcium concentration activates a number of different enzyme systems which lead to new synthesis of RNA, protein and IL-2. FK 506 blocks translocation of the pre-existing cytoplasmic component (B) of the nuclear protein NF-AT at the nucleus by acting either on a Ca++ signalling pathway or on translocation following the action of this pathway (arrows). Both components of NF-AT are required for DNA binding and activation of the IL-2 gene. TCR=T cell receptor; DAG=diacylglycerol; PLC=phospholipase C, PKC=protein kinase C; A=induced nuclear component of NF-AT; B=existing cytoplasmic component of NF-AT.
Figure 4
Figure 4
Differential effects of the immunosuppressive macrolides FK 506 and RAPA on T-cell activation and proliferation. FK 506 (and CsA) inhibit pre-transcriptional events in CD4+ T cell activation, resulting in suppression of production of IL-2 and other cytokines. In contrast, RAPA does not impair IL-2 production, IL-2R expression or ligand binding to IL-2R but blocks the response of T-cells to IL-2 and other cytokines (IL-4, IL-6). TCR=T cell receptor; LKR=lymphokine receptor.
See this image and copyright information in PMC

References

    1. Kino T, Hatanaka H, Hashimoto M, Nishiyama M, Goto T, Okuhara M, Kohsaka M, Aoki H, Imanaka H. FK 506, a novel immunosuppressant isolated from Streptomyces. I. Fermentation, isolation and physicochemical and biological characteristics. J Antibiot. 1987;40:1249–1255. - PubMed
    1. Kino T, Hatanaka H, Miyata S, Inamura N, Nishiyama M, Yajima T, Goto T, Okuhara M, Kohsaka M, Aoki H, Ochiai T. FK 506, a novel immunosuppressant isolated from a Streptomyces. II. Immunosuppressive effect of FK 506 in vitro. J Antibiot. 40:1256–1265. - PubMed
    1. Thomson AW. FK 506. How much potential? Immunol Today. 1989;10:6–9. - PubMed
    1. Starzl TE, Fung J, Venkataramanan R, Todo S, Demetris AJ, Jain A. FK 506 for liver, kidney and pancreas transplantation. Lancet. 1989;ii:1000–1004. - PMC - PubMed
    1. Kahan BD, Chang JY, Seghal SN. Preclinical evaluation of a new potent immunosuppressive agent rapamycin. Transplantation. 1991;52:185–191. - PubMed