Abstract
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.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Isomerases / genetics*
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Amino Acid Sequence
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Animals
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Base Sequence
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Blotting, Northern
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Carrier Proteins / genetics*
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Cloning, Molecular
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Cyclophilin C
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Cyclophilins*
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Cyclosporins / metabolism*
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Gene Expression / drug effects
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Interleukin-1 / pharmacology
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Macromolecular Substances
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Mice
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Molecular Sequence Data
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Oligonucleotides / chemistry
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Peptidylprolyl Isomerase
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Phosphoprotein Phosphatases / genetics*
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Phosphoprotein Phosphatases / metabolism
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Protein Binding
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RNA, Messenger / genetics
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Recombinant Fusion Proteins
Substances
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Carrier Proteins
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Cyclosporins
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Interleukin-1
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Macromolecular Substances
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Oligonucleotides
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RNA, Messenger
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Recombinant Fusion Proteins
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Phosphoprotein Phosphatases
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Amino Acid Isomerases
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Cyclophilins
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Cyclophilin C
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Peptidylprolyl Isomerase
Associated data
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GENBANK/M60962
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GENBANK/M64383
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GENBANK/M64384
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GENBANK/M73779
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GENBANK/M74227
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GENBANK/M80185
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GENBANK/S44816
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GENBANK/S44821
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GENBANK/S56137
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GENBANK/S56139