Smith D F, Baggenstoss B A, Marion T N, Rimerman R A
Department of Pharmacology, University of Nebraska Medical Center, Omaha 68198.
J Biol Chem. 1993 Aug 25;268(24):18365-71.
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.
未活化的类固醇受体处于异源寡聚体复合物中，这可能在激素依赖性激活之前稳定部分折叠的受体多肽。热休克蛋白90（Hsp90）是常见的受体成分，热休克蛋白70（hsp70）是孕酮受体的成分；二者似乎作为蛋白质折叠和组装事件的一般介质都很重要。除Hsp90外，哺乳动物类固醇受体复合物还含有一种52 - 59 kDa的蛋白质，它是一种FK506结合亲免蛋白，具有肽基脯氨酰异构酶活性。已鉴定出其他与受体相关的蛋白质，但特征尚不明确。在本研究中，我们获得了两种禽类孕酮受体成分p50和p54的部分氨基酸序列。通过与已知蛋白质的序列比较，它们似乎是亲免蛋白FKBP家族的不同成员。六个p50肽序列与兔FKBP52区域有80%的同一性；七个p54肽序列与兔FKBP52有60%的同一性。p54与受体的相互作用与p50不同，因为其体外结合对孕酮或N - 乙基马来酰亚胺高度敏感。开发了一种抗p54单克隆抗体，可检测兔和人组织中的一种55 kDa蛋白质；在无细胞重组系统中，兔抗原与rFKBP52一起与鸡孕酮受体结合。虽然p50似乎是FKBP52的鸡同源物，但p54可能是FKBP家族的一个新成员，除FKBP52外，它还与孕酮受体相互作用。
