CHARACTERIZA. OF DIF. FORMS OF ALPHA 4 BETA 1 INTEGRIN

细胞黏附在细胞的迁移和放置中起关键作用。 创伤愈合、免疫识别和靶向的研究进展 淋巴细胞转移到感染区域。细胞与细胞的相互作用 细胞外基质分子和与其他细胞的关系是由 细胞表面的受体。整合素是一个受体家族，它可以 识别特定的细胞外基质分子，并介导细胞- 细胞间的相互作用。整合素是含有α和β的二聚体。 亚单位。根据他们的测试版，他们可以分为三个小组 亚单位。在每个亚群中，不同的阿尔法亚单位与一个 常见的β亚基。Beta1亚群包含六个不同的阿尔法 与Beta1相互作用形成具有不同配体的受体的亚基 专一性。这种配基的特异性是由α亚基决定的。 α4beta1是一种在淋巴细胞上发现的多功能受体，是 只有同时调节细胞-细胞和细胞-基质相互作用的整合素。 靶细胞的溶细胞T细胞识别需要α4β1 淋巴细胞归巢到Peyer‘s斑块。此外，alpha4beta1是 参与控制T细胞增殖。Alpha4beta1似乎 通过增加cAMP水平来响应a的结合而向细胞核发出信号 抑制性T细胞上的配体。CAMP随后抑制IL-2的表达 T细胞增殖所需的受体。 淋巴细胞上的α4beta1异二聚体也是一种受体 细胞外基质蛋白纤维连接蛋白(FN)。它在附近的一个位置绑定FN 它的羧基末端由外显子编码，外显子或者 拼接成信使核糖核酸。该外显子的存在是组织特异性的，而且 在发育过程中的变化表明淋巴细胞与FN的结合可能 在不同的组织和不同的发育阶段都是不同的。 四种不同的转录本来自同一个alpha4基因。一些，如果不是 所有的mRNAs似乎都编码不同形式的α4。我们 假设不同形式的字母4在功能上是不同的 因此，蛋白质解释了阿尔法4的多种功能。 这项建议旨在研究字母4的表达方式 控制住了。这些研究可以分为两部分。第一，表情 并将研究不同α4cDNA的结构。这将是 目的：分离和鉴定白僵菌的α4基因克隆。 由表达四种不同基因的细胞组成的cDNA文库 字母4成绩单。CDNA的序列将与 确定它们编码的蛋白质的结构差异。第二, 我们将克隆alpha4基因的启动子区域，并在 转染法检测转录调控基因的存在 元素。

Cell adhesion is critical in migration and placement of cells during development, in wound healing, immune recognition and targeting of lymphocytes to areas of infection. The interaction of cells with extracellular matrix molecules and with other cells is mediated by receptors on the cell surface. Integrins are a family of receptors that recognize specific extracellular matrix molecules and also mediate cell- cell interactions. Integrins are dimeric containing alpha and beta subunits. They can be divided into three subgroups based on their beta subunits. Within each subgroup, different alpha subunits interact with a common beta subunit. The beta1 subgroup contains six different alpha subunits that interact with beta1 to form receptors with different ligand specificity. This ligand specificity is dictated by the alpha subunit. alpha4beta1 is a multifunctional receptor found on lymphocytes and is the only integrin that mediates both cell-cell and cell-matrix interactions. alpha4beta1 is required for cytolytic T-cell recognition of target cells and homing of lymphocytes to Peyer's patches. In addition, alpha4beta1 is involved in the control of T-cell proliferation. alpha4beta1 appears to signal the nucleus by increasing cAMP levels in response to binding of a ligand on suppressor T-cells. cAMP then inhibits expression of the IL-2 receptor which is required for T-cell proliferation. The alpha4beta1 heterodimer on lymphocytes also acts as a receptor for the extracellular matrix protein fibronectin (FN). It binds FN at a site near its carboxyterminus which is encoded by an exon that is alternatively spliced into mRNA. The presence of this exon is tissue specific and also varies during development suggesting that binding of lymphocytes to FN may vary in different tissues and at different points in development. Four different transcripts arise from a single alpha4 gene. Some, if not all, of the mRNAs appear to encode different forms of alpha4. We hypothesize that the different forms of alpha4 are functionally distinct proteins thus accounting for the multiple functions attributed to alpha4. This proposal is designed to examine how expression of alpha4 is controlled. The studies can be divided into two parts. First, expression and structure of the different alpha4 cDNAs will be examined. This will involve the isolation and characterization of alpha4 cDNA clones from a cDNA library which is made from cells that express the four different alpha4 transcripts. The sequence of the cDNAs will be compared to determine structural differences in the proteins that they encode. Second, we will clone the promoter region of the alpha4 gene and characterize it in transfection assays looking for the presence of transcriptional regulatory elements.