CDNA CLONING AND SEQUENCE-ANALYSIS OF BETA-IG-H3, A NOVEL GENE INDUCED IN A HUMAN ADENOCARCINOMA CELL-LINE AFTER TREATMENT WITH TRANSFORMING GROWTH-FACTOR-BETA
CDNA CLONING AND SEQUENCE-ANALYSIS OF BETA-IG-H3, A NOVEL GENE INDUCED IN A HUMAN ADENOCARCINOMA CELL-LINE AFTER TREATMENT WITH TRANSFORMING GROWTH-FACTOR-BETA
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DOI：
10.1089/dna.1992.11.511
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发表时间：
1992-09-01
影响因子：
3.1
通讯作者：
PURCHIO, AF
中科院分区：
文献类型：
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作者：
SKONIER, J;NEUBAUER, M;PURCHIO, AF
转化生长因子-β（TGF-β）能够影响许多细胞类型的增殖。为了鉴定其蛋白质产物可介导对该因子的细胞应答的新基因，从分离自人肺腺癌细胞系（A549）的mRNA制备cDNA文库，所述人肺腺癌细胞系（A549）已经用TGF-β处理3天。通过差异杂交筛选文库，分离到一个cDNA克隆，即β-ig-h3。在用TGF-β-1处理2天后，该基因在A549细胞中被诱导高达20倍。它还在其他几种细胞系中诱导，包括PC-3和H2981。DNA序列分析表明，β-ig-h3编码一种新的蛋白质β-IG-H3，由683个氨基酸组成，其氨基端含有一个分泌序列，羧基端含有一个Arg-Gly-Asp（RGD）序列，该序列可作为多种整合素的配体识别位点。β-IG-H3还含有与果蝇fasciclin-I中类似区域同源的短氨基酸区域和四个同源内部结构域，其可以折叠成潜在的二价结构，并且可以作为表达适当配体的细胞之间的桥梁。在几种细胞系和组织中检测到β-ig-h3 RNA。用编码β-IG-H3的质粒转染的COS细胞分泌一种主要的68 kD蛋白，该蛋白通过使用抗肽抗体的免疫印迹检测。由于β-Ig-h3在其增殖受TGF-β-1影响的几种细胞系中被诱导，因此它可能参与介导这种多功能生长调节剂的一些信号。
Transforming growth factor-beta (TGF-beta) is capable of affecting the proliferation of many cell types. To identify novel genes whose protein products may mediate cellular responses to this factor, a cDNA library was made from mRNA isolated from a human lung adenocarcinoma cell line (A549) that had been treated for 3 days with TGF-beta. The library was screened by differential hybridization and a cDNA clone, beta-ig-h3, was isolated. This gene was induced up to 20-fold in A549 cells after 2 days of treatment with TGF-beta-1. It was also induced in several other cell lines, including PC-3 and H2981. DNA sequence analysis of beta-ig-h3 indicated that it encoded a novel protein, beta-IG-H3, of 683 amino acids, which contained an amino-terminal secretory sequence and a carboxy-terminal Arg-Gly-Asp (RGD) sequence that can serve as a ligand recognition site for several integrins. Beta-IG-H3 also contained short amino acid regions homologous to similar regions in Drosophila fasciclin-I and four homologous internal domains, which can be folded into a potential bivalent structure and could act as a bridge between cells expressing the appropriate ligand. Beta-ig-h3 RNA was detected in several cell lines and tissues. COS cells transfected with plasmids encoding beta-IG-H3 secreted a major 68-kD protein that was detected by immunoblotting using antipeptide antibodies. Since beta-ig-h3 is induced in several cell lines whose proliferation is affected by TGF-beta-1, it may be involved in mediating some of the signals of this multifunctional growth modulator.