MOLECULAR-CLONING OF THE HUMAN ALPHA-6 INTEGRIN SUBUNIT - ALTERNATIVE SPLICING OF ALPHA-6 MESSENGER-RNA AND CHROMOSOMAL LOCALIZATION OF THE ALPHA-6-GENE AND BETA-4-GENE
MOLECULAR-CLONING OF THE HUMAN ALPHA-6 INTEGRIN SUBUNIT - ALTERNATIVE SPLICING OF ALPHA-6 MESSENGER-RNA AND CHROMOSOMAL LOCALIZATION OF THE ALPHA-6-GENE AND BETA-4-GENE
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DOI：
10.1111/j.1432-1033.1991.tb16140.x
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发表时间：
1991-07-15
期刊：
影响因子：
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通讯作者：
SONNENBERG, A
中科院分区：
文献类型：
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作者：
HOGERVORST, F;KUIKMAN, I;SONNENBERG, A
我们用兔抗α-6多克隆抗体和聚合酶链式反应相结合的方法，从人角质形成细胞的lambda-gt11表达文库中分离到编码α-6亚基的cDNA。该基因编码的α-6亚基由1050个氨基酸组成，胞外有991个氨基酸，跨膜23个氨基酸，胞质36个氨基酸。胞外区含有三个可能的二价阳离子结合部位和九个潜在的N-连接糖基化部位。从正常人乳腺细胞的cDNA文库中分离到两种不同的α-6基因，其中一种与上述基因完全相同。由这两个cDNA编码的两个α-6亚基分别称为α-6A和α-6B，每个亚基都有一个独特的细胞质结构域，α-6B的胞浆结构域比α-6A长18个氨基酸。不同的癌细胞株包含这两个α-6亚基的转录本。K562白血病细胞有少量的α-6A或α-6B基因。肿瘤细胞株的总体表达水平不同，但反映了α-6细胞表面的表达。然而，在A375黑色素瘤细胞中，尽管α-6的mRNA水平很高，但细胞表面的α-6表达很低。这表明，可能还有其他机制参与调节这些细胞表面α-6的表达。这两个α-6亚基的mRNA约为6kb。α-6亚基与整合素家族的其他或亚基相似(与裂解的α亚基的同源性为26-31%)，但它们更类似于α-3亚基(40%的同源性)。这种高度的相似性可能是它们功能相似的基础，因为当与β-1相关时，α-3和α-6亚基都作为层粘连蛋白受体发挥作用，并与层粘连蛋白的长臂结合。阿尔法-6和贝塔-4的基因分别被定位在第二染色体和17q11-QTER上。阿尔法-6和贝塔-4是阿尔法-6与某些上皮细胞结合的替代β亚基。
We have isolated cDNAs encoding the alpha-6 subunit from a lambda-gt11 expression library from human keratinocytes by combined screening with a rabbit polyclonal anti-alpha-6 antibody and the polymerase chain reaction. The alpha-6 subunit encoded by this cDNA consists of 1050 amino acids with a 991-amino-acid extracellular, a 23-amino-acid transmembrane and a 36-amino-acid cytoplasmic domain. The extracellular domain contains three putative divalent cation-binding sites and nine potential N-linked glycosylation sites. From a cDNA library from normal human mammary gland cells two different cDNAs for alpha-6 were isolated, one of which is identical to the above cDNA. The two alpha-6 subunits, called alpha-6A and alpha-6B, encoded by the two cDNAs each have a unique cytoplasmic domain, that of alpha-6B being 18 amino acids longer than that of alpha-6A.Different carcinoma cell lines contain transcripts for both alpha-6 subunits. K562 leukemic cells have little alpha-6A or alpha-6B mRNAs. The overall level of expression varies in the carcinoma cell lines, but reflects alpha-6 cell surface expression. In A375 melanoma cells, however, cell surface expression of alpha-6 was low in spite of a high level of mRNA. This suggests that other mechanisms may be involved in regulating the expression of alpha-6 on the surface of these cells. The mRNA for both alpha-6 subunits is around 6 kb.The alpha-6 subunits are similar to other or subunits (26-31% identity with cleaved a subunits) of the integrin family but they are more similar to the alpha-3 subunit (40% identity). This high degree of similarity may be the basis for their functional resemblance since both alpha-3 and alpha-6 subunits, when associated with beta-1, function as laminin receptors and bind to the long arm of laminin. The genes for alpha-6 and beta-4, the alternative beta-subunit with which alpha-6 combines on certain epithelial cells, were mapped to chromosome 2 and 17q11-qter, respectively.