Regulation of calcineurin phosphatase activity and interaction with the FK-506.FK-506 binding protein complex.

Effect of FK 506 on FK-binding protein and transforming growth factor beta gene expression.

The flexible loop of Bcl-2 is required for molecular interaction with immunosuppressant FK-506 binding protein 38 (FKBP38).

Bcl-2 contains an unusually long loop between the first and the second helices. This loop has been shown to be highly flexible based on NMR and X-ray crystallographic analyses of this region. Bcl-2 is regulated at the posttranslational level through phosphorylation of specific residues within the flexible loop. The biological role and posttranslational modifications of the loop of Bcl-2 is curr...

The immunosuppressive and toxic effects of FK-506 are mechanistically related: pharmacology of a novel antagonist of FK-506 and rapamycin

FK-506 inhibits Ca(2+)-dependent transcription of lymphokine genes in T cells, and thereby acts as a powerful immunosuppressant. However, its potential therapeutic applications may be seriously limited by several side effects, including nephrotoxicity and neurotoxicity. At present, it is unclear whether these immunosuppressive and toxic effects result from interference with related biochemical ...

Regulation of the calmodulin-stimulated protein phosphatase, calcineurin.

The role of protein phosphatases in the regulation of cellular processes is now well established (1, 2). Calcineurin (also called protein phosphatase 2B), a major calmodulin-binding protein in brain and the only serine/threonine protein phosphatase under the control of Ca/calmodulin, plays a critical role in the coupling of Ca signals to cellular responses (3–6). Its stimulation by the multifun...

Independent inhibition of calcineurin and K1 currents by the immunosuppressant FK-506 in rat ventricle

DuBell, W. H., S. T. Gaa, W. J. Lederer, and T. B. Rogers. Independent inhibition of calcineurin and K1 currents by the immunosuppressant FK-506 in rat ventricle. Am. J. Physiol. 275 (Heart Circ. Physiol. 44): H2041–H2052, 1998.—FK-506 increases the cytosolic Ca21 concentration transient in rat ventricular myocytes by prolonging the action potential through inhibition of the K1 currents Ito and...