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

Cell. 1991 Aug 23;66(4):799-806. doi: 10.1016/0092-8674(91)90123-g.

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

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Isomerases / genetics*
  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Blotting, Northern
  • Carrier Proteins / genetics*
  • Cloning, Molecular
  • Cyclophilin C
  • Cyclophilins*
  • Cyclosporins / metabolism*
  • Gene Expression / drug effects
  • Interleukin-1 / pharmacology
  • Macromolecular Substances
  • Mice
  • Molecular Sequence Data
  • Oligonucleotides / chemistry
  • Peptidylprolyl Isomerase
  • Phosphoprotein Phosphatases / genetics*
  • Phosphoprotein Phosphatases / metabolism
  • Protein Binding
  • RNA, Messenger / genetics
  • Recombinant Fusion Proteins

Substances

  • Carrier Proteins
  • Cyclosporins
  • Interleukin-1
  • Macromolecular Substances
  • Oligonucleotides
  • RNA, Messenger
  • Recombinant Fusion Proteins
  • Phosphoprotein Phosphatases
  • Amino Acid Isomerases
  • Cyclophilins
  • Cyclophilin C
  • Peptidylprolyl Isomerase

Associated data

  • GENBANK/M60962
  • GENBANK/M64383
  • GENBANK/M64384
  • GENBANK/M73779
  • GENBANK/M74227
  • GENBANK/M80185
  • GENBANK/S44816
  • GENBANK/S44821
  • GENBANK/S56137
  • GENBANK/S56139