Yuan Q A, Jiang W M, Krissansen G W, Watson J D
Department of Molecular Medicine, School of Medicine, University of Auckland, New Zealand.
Int Immunol. 1990;2(11):1097-108. doi: 10.1093/intimm/2.11.1097.
The integrins have been grouped into three subfamilies based on the utilization of three distinct beta chain subunits, beta 1, beta 2, and beta 3. The recent discovery of beta 4 and beta 5 subunits, and the sharing of alpha subunits between beta subfamilies reflects a greater structural and functional diversity of the integrin supergene family than first anticipated. We exploit integrin gene sequence homology for the identification of a new integrin beta chain. Oligonucleotide probes designed from the highly conserved Arg-Gly-Asp (RGD)-binding domain were used to amplify related transcripts from phytohaemagglutinin-activated human peripheral blood lymphocytes using the polymerase chain reaction (PCR). Five PCR products encoding beta 1, beta 2, beta 3, beta 4, and a new beta clone, designated beta 7, were identified. Full-length beta 7 cDNA was isolated from an activated human T lymphocyte library, using an oligonucleotide probe constructed from the beta 7 PCR product. The beta 7 cDNA contains a long open reading frame of 2391 bp which encodes a protein sequence consisting of 797 amino acids. The encoded sequence revealed a typical signal peptide, a predominantly hydrophilic 707 amino acid residue domain with 8 N-glycosylation sites, a transmembrane domain, and a C-terminal domain of 52 amino acids. The beta 7 sequence showed homology to known beta 1, beta 2, beta 3, beta 4, and beta 5 sequences of 43, 46, 38, 32, and 37% respectively. Four cysteine-rich homologous repeat sequences were found in beta 7 and were homologous to sequences in other integrin beta subunits, and to domain III of the laminin B chains. Part of this cysteine-rich region is homologous to proteins that contain epidermal growth factor-like repeat sequences. Northern analysis revealed that mature beta 7 mRNA is approximately 3.5 kb in size, and expression was restricted to T and B lymphocytes in the small panel of cell types examined. We conclude that beta 7 may be a new member of the leukocyte cell adhesion molecule subset of integrins, and is a candidate immunoregulatory molecule.
基于三种不同的β链亚基β1、β2和β3的利用情况，整合素已被分为三个亚家族。β4和β5亚基的最新发现，以及β亚家族之间α亚基的共享，反映出整合素超基因家族的结构和功能多样性比最初预期的更大。我们利用整合素基因序列同源性来鉴定一种新的整合素β链。从高度保守的精氨酸 - 甘氨酸 - 天冬氨酸（RGD）结合域设计的寡核苷酸探针，用于通过聚合酶链反应（PCR）从植物血凝素激活的人外周血淋巴细胞中扩增相关转录本。鉴定出了五种PCR产物，分别编码β1、β2、β3、β4和一个新的β克隆，命名为β7。使用从β7 PCR产物构建的寡核苷酸探针，从活化的人T淋巴细胞文库中分离出全长β7 cDNA。β7 cDNA包含一个2391 bp的长开放阅读框，其编码一个由797个氨基酸组成的蛋白质序列。编码序列显示出一个典型的信号肽、一个主要为亲水性的707个氨基酸残基结构域，带有8个N - 糖基化位点、一个跨膜结构域和一个52个氨基酸的C末端结构域。β7序列与已知的β1、β2、β3、β4和β5序列的同源性分别为43%、46%、38%、32%和37%。在β7中发现了四个富含半胱氨酸的同源重复序列，它们与其他整合素β亚基中的序列以及层粘连蛋白B链的结构域III同源。这个富含半胱氨酸区域的一部分与包含表皮生长因子样重复序列的蛋白质同源。Northern分析表明，成熟的β7 mRNA大小约为3.5 kb，在所检测的一小部分细胞类型中，其表达仅限于T淋巴细胞和B淋巴细胞。我们得出结论，β7可能是整合素白细胞细胞粘附分子亚群的一个新成员，并且是一种候选免疫调节分子。
