« Previous AbstractCharacterization of compost biofiltration media    Next AbstractDevelopment of a potential probiotic fresh cheese using two Lactobacillus salivarius strains isolated from human milk »

EMBO J

Title:		Immunophilins interact with calcineurin in the absence of exogenous immunosuppressive ligands
Author(s):		Cardenas ME; Hemenway C; Muir RS; Ye R; Fiorentino D; Heitman J;
Address:		"Department of Genetics, Duke University Medical Center, Durham, NC 27710"
Journal Title:		EMBO J
Year:		1994
Volume:		13
Issue:		24
Page Number:		5944 - 5957
DOI:		10.1002/j.1460-2075.1994.tb06940.x
ISSN/ISBN:		0261-4189 (Print) 1460-2075 (Electronic) 0261-4189 (Linking)
Abstract:		"The peptidyl-prolyl isomerases FKBP12 and cyclophilin A (immunophilins) form complexes with the immunosuppressants FK506 and cyclosporin A that inhibit the phosphatase calcineurin. With the yeast two hybrid system, we detect complexes between FKBP12 and the calcineurin A catalytic subunit in both the presence and absence of FK506. Mutations in FKBP12 surface residues or the absence of the calcineurin B regulatory subunit perturb the FK506-dependent, but not the ligand-independent, FKBP12-calcineurin complex. By affinity chromatography, both FKBP12 and cyclophilin A bind calcineurin A in the absence of ligand, and FK506 and cyclosporin A respectively potentiate these interactions. Both in vivo and in vitro, the peptidyl-prolyl isomerase active sites are dispensable for ligand-independent immunophilin-calcineurin complexes. Lastly, by genetic analyses we demonstrate that FKBP12 modulates calcineurin functions in vivo. These findings reveal that immunophilins interact with calcineurin in the absence of exogenous ligands and suggest that immunosuppressants may take advantage of the inherent ability of immunophilins to interact with calcineurin"
Keywords:		"Amino Acid Isomerases/genetics/*metabolism Base Sequence Calcineurin Calmodulin-Binding Proteins/*metabolism Carrier Proteins/genetics/*metabolism Chromatography, Affinity Cyclosporine/genetics/*metabolism/pharmacology DNA-Binding Proteins/genetics/*metab;"
Notes:		"MedlineCardenas, M E Hemenway, C Muir, R S Ye, R Fiorentino, D Heitman, J eng ES07031/ES/NIEHS NIH HHS/ Comparative Study Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. England 1994/12/15 EMBO J. 1994 Dec 15; 13(24):5944-57. doi: 10.1002/j.1460-2075.1994.tb06940.x"