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PMID: 1279700 Published · ppublish English Comparative Study Journal Article Research Support, U.S. Gov't, P.H.S.

Expression and characterization of human FKBP52, an immunophilin that associates with the 90-kDa heat shock protein and is a component of steroid receptor complexes.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 89 ·No. 22 ·1992-11-15 ·Pages 10974-8

Peattie DA, Harding MW, Fleming MA, DeCenzo MT, Lippke JA, Livingston DJ, Benasutti M

Abstract

Using an FK506 affinity column to identify mammalian immunosuppressant-binding proteins, we identified an immunophilin with an apparent M(r) approximately 55,000, which we have named FKBP52. We used chemically determined peptide sequence and a computerized algorithm to search GenPept, the translated GenBank data base, and identified two cDNAs likely to encode the murine FKBP52 homolog. We amplified a murine cDNA fragment, used it to select a human FKBP52 (hFKBP52) cDNA clone, and then used the clone to deduce the hFKBP52 sequence (calculated M(r) 51,810) and to express hFKBP52 in Escherichia coli. Recombinant hFKBP52 has peptidyl-prolyl cis-trans isomerase activity that is inhibited by FK506 and rapamycin and an FKBP12-like consensus sequence that probably defines the immunosuppressant-binding site. FKBP52 is apparently common to several vertebrate species and associates with the 90-kDa heat shock protein (hsp90) in untransformed mammalian steroid receptor complexes. The putative immunosuppressant-binding site is probably distinct from the hsp90-binding site, and we predict that FKBP52 has different structural domains to accommodate these functions. hFKBP52 contains 12 protein kinase phosphorylation-site motifs and a potential calmodulin-binding site, implying that posttranslational phosphorylation could generate multiple isoforms of the protein and that calmodulin and intracellular Ca2+ levels could affect FKBP52 function. FKBP52 transcripts are present in a variety of human tissues and could vary in abundance and/or stability.

MeSH Terms
Amino Acid Isomerases/genetics,isolation & purification,metabolism Amino Acid Sequence Base Sequence Binding Sites Blotting, Northern Carrier Proteins/genetics,isolation & purification,metabolism Cloning, Molecular Escherichia coli/genetics Heat-Shock Proteins/genetics,isolation & purification,metabolism Humans Macromolecular Substances Molecular Sequence Data Molecular Weight Oligodeoxyribonucleotides Organ Specificity Peptidylprolyl Isomerase RNA Probes Receptors, Steroid/metabolism Recombinant Proteins/isolation & purification,metabolism Restriction Mapping Sequence Homology, Amino Acid Tacrolimus/metabolism Transcription, Genetic
Chemicals
Carrier Proteins Heat-Shock Proteins Macromolecular Substances Oligodeoxyribonucleotides RNA Probes Receptors, Steroid Recombinant Proteins Amino Acid Isomerases Peptidylprolyl Isomerase Tacrolimus
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Peattie D A
Vertex Pharmaceuticals Incorporated, Cambridge, MA 02139-4211.
Harding M W
Fleming M A
DeCenzo M T
Lippke J A
Livingston D J
Benasutti M
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48 references, click to expand
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.89.22.10974
Published
1992-11-15
Pages
10974-8
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC50465
Subset
IM
Grants
NIAID NIH HHS · AI29804 · United States
Databases
GENBANK
M88279
External Links
PubMed source DOI: 10.1073/pnas.89.22.10974 PMC Full Text View journal details
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