Inhibition of calcineurin by cyclosporin A-cyclophilin requires calcineurin B

• Published in: FEBS letters Vol. 314; no. 1; pp. 37 - 40
• Main Authors: Haddy, Alice, Swanson, Selene K.-H., Born, Timothy L., Rusnak, Frank
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 07.12.1992; Elsevier
• Subjects: Amino Acid Isomerases - pharmacology; Biological and medical sciences; Calcineurin; calcineurin A; calcineurin B; calmodulin; Calmodulin-Binding Proteins - drug effects; Calmodulin-Binding Proteins - genetics; CaM; Carrier Proteins - pharmacology; Caseins - metabolism; CNA; CNB; CsA; Cyclophilin; Cyclosporin A; Cyclosporine - pharmacology; Cyclosporins - pharmacology; CyP; Dose-Response Relationship, Drug; FK506 binding protein; FKBP; hCyPA; hCyPB; Humans; Immunomodulators; Immunosuppression; Medical sciences; Nitrophenols - metabolism; Organophosphorus Compounds - metabolism; Peptidylprolyl Isomerase; Pharmacology. Drug treatments; Phosphoprotein Phosphatases - drug effects; Phosphoprotein Phosphatases - genetics; Phosphoprotein Phosphatases - metabolism; protein phosphatase; rCNA; recombinant calcineurin A; recombinant human cyclophilin A; recombinant human cyclophilin B; Recombinant Proteins - drug effects; Structure-Activity Relationship; PP; Calcineurin; hCyPB; Cyclosporin A; CN; CaM; CsA; rCNA; Immunosuppression; FKBP; Cyclophilin; CNB; hCyPA; CNA; CyP; Enzymatic activity; Enzyme; Phosphoprotein phosphatase; Immunosuppressive agent; Mechanism of action; In vitro; Biological receptor
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/0014-5793(92)81456-V

The interaction of the immunosuppressive complex cyclosporin A-cyclophilin (CsA-CyP) with the Ca 2+/calmodulin-dependent protein phosphatase calcineurin is investigated using a recombinant form of the A subunit of calcineurin (rCNA). Only in the presence of purified calcineurin B (CNB) does rCNA show the response of native calcineurin, i.e. 50% inhibition of rCNA phosphatase activity at 6 nM human cyclophilin B and 0.6 μM human cyclophilin A using [ 32P]casein as substrate, yet stimulation of activity with p-nitrophenyl phosphate as substrate. This study demonstrates that the B subunit is necessary to confer sensitivity of calcineurin to CsA-CyP.