Cyclophilin-40, a protein with homology to the P59 component of the steroid receptor complex. Cloning of the cDNA and further characterization

L. J. Kieffer, T. W. Seng, W. Li, D. G. Osterman, R. E. Handschumacher, R. M. Bayney

Research output: Contribution to journalArticle

115 Scopus citations

Abstract

We have reported previously the isolation and preliminary characterization of a 40-kDa cyclosporin A (CsA)-binding protein, cyclophilin-40 (CyP-40). To determine the sequence of this protein, degenerate oligonucleotide primers based on bovine brain CyP-40 tryptic peptides were used to generate a polymerase chain reaction fragment of CyP-40 cDNA. This was used to isolate the complete cDNA from a human pancreatic islet cell library. Northern analysis indicated ubiquitous distribution of CyP-40 mRNA throughout human tissues. The CyP-18 domain of CyP-40 is most similar to maize CyP (64.3% identity), whereas 150 amino acids of the non-CyP-18 domain of CyP-40 share 30.7% identity with P59, a member of the steroid receptor complex. Failure to detect glycosylation and mass spectroscopy with isolated CyP-40 indicate minimal, if any, posttranslational modification. Employing a new assay for calcineurin protein phosphatase activity to compare the effects of CyP-40 · CsA and CyP-18 · CsA complexes, IC50 values of 320 nM ± 20 and 195 nM ± 15, respectively, were obtained. A chemical cross-linking study revealed that CyP-40 competes for 125I-CyP-18 binding to calcineurin in the presence of CsA. The homology of CyP-40 to P59 suggests that CyP-40 might be involved in modulating the activity of biologically important receptors.

Original languageEnglish (US)
Pages (from-to)12303-12310
Number of pages8
JournalJournal of Biological Chemistry
Volume268
Issue number17
StatePublished - 1993

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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