THE HUMAN ANDROGEN RECEPTOR - COMPLEMENTARY DEOXYRIBONUCLEIC-ACID CLONING, SEQUENCE-ANALYSIS AND GENE-EXPRESSION IN PROSTATE

THE HUMAN ANDROGEN RECEPTOR - COMPLEMENTARY DEOXYRIBONUCLEIC-ACID CLONING, SEQUENCE-ANALYSIS AND GENE-EXPRESSION IN PROSTATE
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DOI:
10.1210/mend-2-12-1265
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发表时间:
1988-12-01
影响因子:
--
通讯作者:
WILSON, EM
WILSON, EM
中科院分区:
医学2区
文献类型:
--
作者:
LUBAHN, DB;JOSEPH, DR;WILSON, EM

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雄激素通过高亲和力受体蛋白介导其对雄性性分化和发育的作用。我们在这里报告的人雄激素受体(hAR)的完整编码序列的克隆。通过序列同源性,hAR是核受体家族的成员,与孕酮、盐皮质激素和糖皮质激素受体具有最接近的序列同一性。同源性最高的区域包括DNA结合结构域和疏水配体结合结构域内的小区域。比较推导的919个氨基酸序列的hAR(98,999摩尔重量)的902个氨基酸序列的大鼠AR(98,227摩尔重量)揭示了相同的序列中的DNA和酶结合域,与85%的总体同源性。在人前列腺中,主要的雄激素受体mRNA种类是10种脱氢酶,而丰度较低的mRNA是大约7种脱氢酶。针对来自hAR的N-末端区域的合成肽产生兔多克隆抗体。人前列腺组织的免疫细胞化学分析表明,AR主要定位于腺上皮细胞的细胞核。
Androgenic hormones mediate their effects on male sex differentiation and development through a high affinity receptor protein. We report here cloning of the complete coding sequence of the human androgen receptor (hAR). By sequence homology hAR is a member of the nuclear receptor family, with closest sequence identity to the progesterone, mineralocorticoid, and glucocorticoid receptors. Regions of highest homology include the DNA-binding domain and a small region within the hydrophobic ligand-binding domain. Comparison of the deduced 919 amino acid sequence of hAR (98,999 mol wt) to the 902 amino acid sequence of rat AR (98,227 mol wt) reveals identical sequences in the DNA- and hormone-binding domains, with an overall homology of 85%. In human prostate, the major androgen receptor mRNA species is 10 kilobases while a less abundant mRNA is approximately 7 kilobases. Rabbit polyclonal antibodies were raised against a synthetic peptide from the N-terminal region of hAR. Immunocytochemical analysis of human prostate tissue demonstrated that AR is localized predominantly in nuclei of glandular epithelial cells.