Rabbit FKBP-59/HBI does not inhibit calcineurin activity in vitro.
The effect of recombinant FKBP-59/HBI or of its first N-terminal domain FKBP-59/HBI-I on the phosphatase activity of calcineurin (a Ca(+2)-calmodulin dependent phosphatase) was tested in vitro in the presence or absence of the immunosuppressant drug FK506. Contrarily to the inhibition observed with the immunosuppressant complex FKBP-12-FK506, no significant inhibition was observed with FKBP-59/HBI or FKBP-59/HBI-I in the presence of FK506, even though FKBP-59/HBI-1 is nearly 55% homologous to the immunophilin FKBP-12. Inhibition was tested both with native calcineurin (calcineurin A: Mr 58-59 kDa) and with protease activated, calmodulin independent calcineurin (calcineurin A: Mr 45 kDa). There was no competitive effect of FKBP-59 on the inhibitory activity of the FKBP-12-FK506 complex, even when the molar concentration of FKBP-59/HBI was 100 times higher than that of FKBP-12. Clearly, although the first domain of FKBP-59/HBI displays several structural and functional features of FKBP-12, it does not interact with calcineurin.
Lebeau
M C
MC
INSERM U33, Le Kremlin Bicêtre, France.
Myagkikh
I
I
Rouvière-Fourmy
N
N
Baulieu
E E
EE
Klee
C B
CB
D000595:Amino Acid Sequence; D000818:Animals; D019703:Calcineurin; D002148:Calmodulin-Binding Proteins / Q000037:antagonists & inhibitors*; D002352:Carrier Proteins / Q000737:chemistry / Q000494:pharmacology*; D006360:Heat-Shock Proteins / Q000737:chemistry / Q000494:pharmacology*; D008969:Molecular Sequence Data; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors*; D011817:Rabbits; D011994:Recombinant Proteins / Q000737:chemistry / Q000494:pharmacology; D016559:Tacrolimus / Q000494:pharmacology; D022021:Tacrolimus Binding Proteins
D002148:Calmodulin-Binding Proteins; D002352:Carrier Proteins; D006360:Heat-Shock Proteins; D011994:Recombinant Proteins; D019703:Calcineurin; D010749:Phosphoprotein Phosphatases; D022021:Tacrolimus Binding Proteins; D016559:Tacrolimus