Inhibition of calcineurin by cyclosporin A‐cyclophilin requires calcineurin B

[摘要]

The interaction of the immunosuppressive complex cyclosporin A-cyclophilin (CsA-CyP) with the Ca²⁺/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.

[学科分类] 生物化学/生物物理

[关键词] Calcineurin;Cyclosporin A;Cyclophilin;Immunosuppression;CaM;calmodulin;CN;calcineurin;CNA;calcineurin A;CNB;calcineurin B;CsA;cyclosporin A;CyP;cyclophilin;hCyPA;recombinant human cyclophilin A;FKBP;FK506 binding protein;hCyPB;recombinant human cyclophilin B;PP;protein phosphatase;rCNA;recombinant calcineurin A