FKBP, the binding protein for the immunosuppressive drug, FK-506, is not an inhibitor of protein kinase C activity.
Recently, the amino acid sequence of a 12 Kd endogenous protein inhibitor of protein kinase C (PKC-I 2) has been shown to be identical to that of the 12 KDa receptor for the immunosuppressive drug, FK-506. In view of this observation we examined the effects of recombinant and native human FKBP on protein kinase C (PKC) activity. FKBP, at molar concentrations up to 1900-fold over that of PKC, failed to inhibit PKC phosphorylation of histone H1 and failed to block the auto-phosphorylation of PKC. Interestingly, FKBP is phosphorylated by PKC in these reactions. The phosphorylation of FKBP by PKC appears to be specific since the catalytic subunit of cAMP-dependent protein kinase fails to phosphorylate the binding protein. Our results fail to support a role for FKBP as an inhibitor of protein kinase C.
Cryan
J
J
Department of Immunology Research Merck, Sharp and Dohme Research Laboratories, Rahway, New Jersey.
Hung
S H
SH
Wiederrecht
G
G
Sigal
N H
NH
Siekierka
J J
JJ
D000818:Animals; D001921:Brain / Q000201:enzymology; D002118:Calcium / Q000494:pharmacology; D002352:Carrier Proteins / Q000378:metabolism / Q000494:pharmacology*; D002417:Cattle; D006657:Histones; D006801:Humans; D007700:Kinetics; D010718:Phosphatidylserines / Q000494:pharmacology; D010766:Phosphorylation; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism / Q000494:pharmacology; D016559:Tacrolimus / Q000378:metabolism*; D022021:Tacrolimus Binding Proteins
D002352:Carrier Proteins; D006657:Histones; D010718:Phosphatidylserines; D011994:Recombinant Proteins; D011493:Protein Kinase C; D022021:Tacrolimus Binding Proteins; D002118:Calcium; D016559:Tacrolimus