STRUCTURE AND EXPRESSION OF THE GENES-CODING FOR HUMAN ALPHA-1-ACID GLYCOPROTEIN

STRUCTURE AND EXPRESSION OF THE GENES-CODING FOR HUMAN ALPHA-1-ACID GLYCOPROTEIN
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DOI:
10.1002/j.1460-2075.1987.tb02503.x
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发表时间:
1987-08-01
期刊:
影响因子:
11.4
通讯作者:
CORTESE, R
CORTESE, R
中科院分区:
生物学1区
文献类型:
--
作者:
DENTE, L;PIZZA, MG;CORTESE, R

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.alpha。1-酸性糖蛋白(. α . agp)是一种特征明确的人血浆蛋白。其结构特性已被研究多年,但对其功能却知之甚少。纯化人α -氨基酸序列分析。从几个个体汇集的血浆中提取的AGP显示出相当大的异质性。我们已经克隆了编码。alpha的基因组DNA片段。我们证明它包含三个相邻的。AGP编码区AGP- a, B和B”外显子-内含子组织相同,但编码电位略有不同。这些结果解释了蛋白质测序观察到的异质性。Southern blot分析表明克隆的聚类包含所有的。人类基因组中的AGP编码序列。大多数。alpha。人肝脏中AGP mRNA是由AGP- a转录而来,其启动子和帽位已经确定,而人肝脏中AGP-B和B”mRNA的表达水平很低。我们以Hep3B肝癌细胞为模型系统进行急性期反应的体外研究,发现LPS刺激单核细胞培养液只对AGP-A有强烈的诱导作用。
.alpha.1-acid glycoprotein (.alpha.AGP) is a well-characterized human plasma protein. Its structural properties have been studied for many years but little is known about its function. Amino acid sequence analysis of purified human .alpha.AGP from plasma pooled from several individuals showed considerable heterogeneity. We have cloned the genomic DNA segment encoding .alpha.AGP and we show that it contains three adjacent .alpha.AGP coding regions, AGP-A, B and B'', identical in exon-intron organization but with slightly different coding potential. These results account for the heterogeneity observed by protein sequencing. Southern blot analysis indicates that the cloned cluster contains all the .alpha.AGP coding sequences present in the human genome. The larger majority of .alpha.AGP mRNA in human liver is transcribed from AGP-A, whose promoter and cap site have been determined while the level of AGP-B and B'' mRNA in human liver is very low. Using Hep3B hepatoma cells as a model system for the in vitro study of the acute phase reaction, we show that only AGP-A is strongly induced by treatment with culture medium of LPS stimulated monocytes.