Two cytoplasmic candidates for immunophilin action are revealed by affinity for a new cyclophilin: one in the presence and one in the absence of CsA.
We report the cloning and characterization of a new binding protein for the immunosuppressive drug cyclosporin A (CsA). This new cyclophilin, cyclophilin C (cyp C), shows extensive homology with all previously identified cyclophilins. Cyp C mRNA is expressed in a restricted subset of tissues relative to cyclophilins A and B, but is present in those tissues reported to be most affected by CsA therapy. A cyp C fusion protein has peptidyl-prolyl isomerase activity, and CsA inhibits this activity. Using the cyp C fusion protein as an affinity ligand to probe cellular extracts, we find that the cyp C fusion protein binds specifically to a 77 kd protein in the absence of CsA, while in the presence of CsA it instead binds specifically to a 55 kd protein. We propose that the p77 is involved in cyp C native function and that the p55 is involved in signal transduction events blocked by treatment with immunosuppressive levels of CsA.
Friedman
J
J
Department of Pathology, Howard Hughes Medical Institute, Stanford University School of Medicine, California 94305.
Weissman
I
I
D000591:Amino Acid Isomerases / Q000235:genetics*; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D002352:Carrier Proteins / Q000235:genetics*; D003001:Cloning, Molecular; D000072622:Cyclophilin C; D021983:Cyclophilins; D003524:Cyclosporins / Q000378:metabolism*; D015870:Gene Expression / Q000187:drug effects; D007375:Interleukin-1 / Q000494:pharmacology; D046911:Macromolecular Substances; D051379:Mice; D008969:Molecular Sequence Data; D009841:Oligonucleotides / Q000737:chemistry; D019696:Peptidylprolyl Isomerase; D010749:Phosphoprotein Phosphatases / Q000235:genetics* / Q000378:metabolism; D011485:Protein Binding; D012333:RNA, Messenger / Q000235:genetics; D011993:Recombinant Fusion Proteins
D002352:Carrier Proteins; D003524:Cyclosporins; D007375:Interleukin-1; D046911:Macromolecular Substances; D009841:Oligonucleotides; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D010749:Phosphoprotein Phosphatases; D000591:Amino Acid Isomerases; D021983:Cyclophilins; D000072622:Cyclophilin C; D019696:Peptidylprolyl Isomerase