Abstract: The cloning and characterization of a new binding protein class, cyclophilin C (cyp C) and homologous proteins, is provided which is capable of binding to, e.g., the immunosuppressive drug cyclosporin A (CsA). The pattern of cyp C mRNA expression differs from that of cyp A mRNA expression, with cyp C being expressed in a more restricted subset of tissues, including those tissues reported to be most affected by CsA therapy. A fusion protein containing, e.g., amino acids 16-212 of cyp C has peptidyl-prolyl-isomerase activity (PPIase), and CsA inhibits this activity. Most significantly, these cyp C fusion proteins can be used as ligands for the identification of intracellular proteins which together form high affinity associations. For example, the cyp C fusion protein binds specifically to a protein of 77 Kd in the absence of CsA, while in the presence of CsA it no longer binds to this p77, but instead binds specifically to a protein 55 Kd, identified as calcineurin.

Abstract: A method of evaluating the immunosuppressive activity of a compound including contacting the compound with calcineurin and determining the ability of the compound to bind to the calcineurin. The ability to bind to the calcineurin is positively correlated to the immunosuppressive activity of the compound.

Abstract: An expression system for recombinant production of a desired protein comprises CHO cells transformed with a DNA sequence having the desired protein coding sequence under control of the human metallothionein-II promoter. The cells can be maintained on serum-free medium and induced in the presence of an induction mediator. In addition, the system may include an enhancer element and/or a resistance-conferring gene to provide increased levels of expression. The system can process genomic as well as intronless DNA, and is capable of producing proteins which have the same characteristics as those obtained from native sources. Human growth hormone which is indistinguishable from that produced by the pituitary has been thus produced.