Inhibition of calcineurin by cyclosporin A-cyclophilin requires calcineurin B.
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 microM 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.
Haddy
A
A
Section of Hematology Research, Mayo Foundation, Rochester, MN 55905.
Swanson
S K
SK
Born
T L
TL
Rusnak
F
F
D000591:Amino Acid Isomerases / Q000494:pharmacology*; D019703:Calcineurin; D002148:Calmodulin-Binding Proteins / Q000187:drug effects* / Q000235:genetics; D002352:Carrier Proteins / Q000494:pharmacology*; D002364:Caseins / Q000378:metabolism; D016572:Cyclosporine / Q000494:pharmacology*; D003524:Cyclosporins / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D009596:Nitrophenols / Q000378:metabolism; D009943:Organophosphorus Compounds / Q000378:metabolism; D019696:Peptidylprolyl Isomerase; D010749:Phosphoprotein Phosphatases / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000187:drug effects; D013329:Structure-Activity Relationship
D002148:Calmodulin-Binding Proteins; D002352:Carrier Proteins; D002364:Caseins; D003524:Cyclosporins; D009596:Nitrophenols; D009943:Organophosphorus Compounds; D011994:Recombinant Proteins; C008644:nitrophenylphosphate; D016572:Cyclosporine; D019703:Calcineurin; D010749:Phosphoprotein Phosphatases; D000591:Amino Acid Isomerases; D019696:Peptidylprolyl Isomerase