Two FKBP-related proteins are associated with progesterone receptor complexes.
Unactivated steroid receptors are in heterooligomeric complexes that perhaps stabilize a partially folded receptor polypeptide prior to hormone-dependent activation. Hsp90 is a common receptor component and hsp70 is a component of progesterone receptors; both appear to be important as general mediators of protein folding and assembly events. In addition to hsp90, mammalian steroid receptor complexes contain a 52-59-kDa protein that is an FK506-binding immunophilin and has peptidyl-prolyl isomerase activity. Other receptor-associated proteins have been identified but not well-characterized. In the present study, we obtained partial amino acid sequences for two avian progesterone receptor components, p50 and p54. From sequence comparisons with known proteins, they appear to be distinct members of the FKBP family of immunophilins. Six p50 peptide sequences have 80% identity with regions of rabbit FKBP52; seven p54 peptide sequences have 60% identity with rabbit FKBP52. Interaction of p54 with receptor is distinct from p50 in that its binding in vitro is highly sensitive to progesterone or N-ethylmaleimide. An anti-p54 monoclonal antibody was developed that detects a 55-kDa protein in rabbit and human tissues; in a cell-free reconstitution system, the rabbit antigen binds to chicken progesterone receptor along with rFKBP52. While p50 appears to be the chicken homolog of FKBP52, p54 is perhaps a novel member of the FKBP family that, in addition to FKBP52, interacts with progesterone receptor.
Smith
D F
DF
Department of Pharmacology, University of Nebraska Medical Center, Omaha 68198.
Baggenstoss
B A
BA
Marion
T N
TN
Rimerman
R A
RA
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal; D015153:Blotting, Western; D002352:Carrier Proteins / Q000302:isolation & purification / Q000378:metabolism*; D002645:Chickens; D003600:Cytosol / Q000378:metabolism; D015180:Electrophoresis, Gel, Two-Dimensional; D004591:Electrophoresis, Polyacrylamide Gel; D004967:Estrogens / Q000494:pharmacology; D005033:Ethylmaleimide / Q000494:pharmacology; D005260:Female; D008322:Mammals; D008969:Molecular Sequence Data; D010057:Oviducts / Q000187:drug effects / Q000378:metabolism*; D010446:Peptide Fragments / Q000302:isolation & purification; D011374:Progesterone / Q000494:pharmacology; D011980:Receptors, Progesterone / Q000302:isolation & purification* / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D016559:Tacrolimus / Q000378:metabolism; D022021:Tacrolimus Binding Proteins
D000911:Antibodies, Monoclonal; D002352:Carrier Proteins; D004967:Estrogens; D010446:Peptide Fragments; D011980:Receptors, Progesterone; D011374:Progesterone; D022021:Tacrolimus Binding Proteins; D005033:Ethylmaleimide; D016559:Tacrolimus