FAP48, a new protein that forms specific complexes with both immunophilins FKBP59 and FKBP12. Prevention by the immunosuppressant drugs FK506 and rapamycin.
We have identified a human gene encoding a 48-kDa protein that specifically interacts with the peptidyl prolyl isomerase FK506-binding protein 59 (FKBP59) and also with the well known FKBP12. FKBP59 and FKBP12 belong to the large family of immunophilins that bind the macrolide immunosuppressant drugs FK506 and rapamycin. The yeast two-hybrid system was used to isolate target proteins that interact with the immunosuppressant drug binding domain of the rabbit FKBP59. The cDNA for an as yet unidentified protein was isolated and cloned from a Jurkat cell library. The cDNA sequence of 1804 base pairs reveals an open reading frame of 417 amino acids. In vitro experiments suggest a direct interaction between FKBP59 and this new target protein. This specific association seems to be restricted to the FKBP family, since it also occurs both in vivo and in vitro with FKBP12 but not with cyclophilin 40. This novel protein was named FKBP-associated protein (FAP48). The formation of the complexes between FKBP59 or FKBP12 and FAP48 is prevented by FK506 and rapamycin in a dose-dependent manner. These results suggest that FAP48 shares or overlaps the macrolide binding site on FKBP59 as well as on FKBP12 and therefore may represent a natural common ligand of these immunosuppressant drug receptors.
Chambraud
B
B
INSERM (U33) and Collège de France, 80 rue du Général Leclerc, 94276 Bicêtre Cédex, France.
Radanyi
C
C
Camonis
J H
JH
Shazand
K
K
Rajkowski
K
K
Baulieu
E E
EE
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D001483:Base Sequence; D001667:Binding, Competitive; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D003001:Cloning, Molecular; D004268:DNA-Binding Proteins / Q000378:metabolism*; D015870:Gene Expression; D006360:Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology; D046911:Macromolecular Substances; D008969:Molecular Sequence Data; D011090:Polyenes / Q000494:pharmacology*; D011485:Protein Binding / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics; D011817:Rabbits; D020123:Sirolimus; D016559:Tacrolimus / Q000494:pharmacology*; D022021:Tacrolimus Binding Proteins; D014407:Tumor Cells, Cultured
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; C103024:GLMN protein, human; D006360:Heat-Shock Proteins; D007166:Immunosuppressive Agents; D046911:Macromolecular Substances; D011090:Polyenes; D012333:RNA, Messenger; D022021:Tacrolimus Binding Proteins; D020123:Sirolimus; D016559:Tacrolimus