Tacrolimus (FK-506) is a drug that inhibits an enzyme called calcineurin. Calcineurin is a protein phosphatase. This is an enzyme that dephosphorylates (removes phosphate groups) from proteins. When added to cells, tacrolimus can inhibit the dephosphorylation of a protein called NFAT, but it cannot prevent the dephosphorylation of a protein called CDK1. What is the most likely explanation for this finding

Basically, calcineurin is an enzyme which dephosphorylates the proteins and tacrolimus is working against the calcineurin and it inhibits the action of calcineurin or we can say that it inhibits the dephosphorylation of protein.

Now, calcineurin acts on NFAT because it is substrate for calcineurin enzyme but it does not act on CDK1 as it is not substrate for calcineurin.

That's why, tacrolimus is an inhibitor of enzyme calcineurin and it will prevent the dephosphorylation of NFAT protein but it cannot prevent the dephosphorylation of CDK1 because it is not substrate for calcineurin.

the endomembrane system i think