Arnaout M A, Remold-O'Donnell E, Pierce M W, Harris P, Tenen D G
Renal Division, Children's Hospital, Boston, MA.
Proc Natl Acad Sci U S A. 1988 Apr;85(8):2776-80. doi: 10.1073/pnas.85.8.2776.
The cell-surface glycoprotein Mo1 is a member of the family of leukocyte cell adhesion molecules (Leu-CAMs) that includes lymphocyte function-associated antigen 1 (LFA-1) and p150,95. Each Leu-CAM is a heterodimer with a distinct alpha subunit noncovalently associated with a common beta subunit. Leu-CAMs play crucial roles in cell-cell and cell-matrix interactions. We describe the isolation and analysis of two partial cDNA clones encoding the alpha subunit of the Leu-CAM Mo1 in humans and guinea pigs. A monoclonal antibody directed against an epitope in the carboxyl-terminal portion of the guinea pig alpha chain was used for immunoscreening a lambda gt11 expression library. The sequence of a 378-base-pair insert from one immunoreactive clone revealed a single continuous open reading frame encoding 126 amino acids including a 26-amino acid tryptic peptide isolated from the purified guinea pig alpha subunit. A cDNA clone of identical size was isolated from a human monocyte/lymphocyte cDNA library by using the guinea pig clone as a probe. The human clone also encoded a 126-amino acid peptide including the sequence of an additional tryptic peptide present in purified human Mo1 alpha chain. RNA gel blots revealed that mature Mo1 alpha chain mRNA is approximately 5 kilobases in guinea pigs and humans. Southern analysis of DNA from hamster-human hybrids localized the human Mo1 alpha chain to chromosome 16, which has been shown to contain the gene for the alpha chain of lymphocyte function-associated antigen 1. A comparison of the Mo1 alpha chain coding region revealed significant homologies with carboxyl-terminal portions of the alpha subunits of fibronectin, vitronectin, and platelet IIb/IIIa receptors. These data suggest that the alpha subunits of Leu-CAMs evolved by gene duplication from a common ancestral gene and strengthen the hypothesis that the alpha subunits of these heterodimeric cell adhesion molecules on myeloid and lymphoid cells, platelets, and fibroblasts are evolutionary related.
细胞表面糖蛋白Mo1是白细胞细胞黏附分子（Leu-CAMs）家族的成员，该家族包括淋巴细胞功能相关抗原1（LFA-1）和p150,95。每个Leu-CAM都是一个异二聚体，由一个独特的α亚基与一个共同的β亚基非共价结合而成。Leu-CAMs在细胞间和细胞与基质的相互作用中起关键作用。我们描述了在人和豚鼠中编码Leu-CAM Mo1α亚基的两个部分cDNA克隆的分离和分析。一种针对豚鼠α链羧基末端部分表位的单克隆抗体用于免疫筛选λgt11表达文库。来自一个免疫反应性克隆的378个碱基对插入片段的序列显示有一个单一的连续开放阅读框，编码126个氨基酸，包括从纯化的豚鼠α亚基中分离出的一个26个氨基酸的胰蛋白酶肽段。通过使用豚鼠克隆作为探针，从人单核细胞/淋巴细胞cDNA文库中分离出一个大小相同的cDNA克隆。人克隆也编码一个126个氨基酸的肽段，包括纯化的人Mo1α链中存在的另一个胰蛋白酶肽段的序列。RNA凝胶印迹显示，成熟的Mo1α链mRNA在豚鼠和人中约为5千碱基。对仓鼠-人杂种DNA的Southern分析将人Mo1α链定位于16号染色体，该染色体已被证明含有淋巴细胞功能相关抗原1α链的基因。对Mo1α链编码区的比较显示，它与纤连蛋白、玻连蛋白和血小板IIb/IIIa受体α亚基的羧基末端部分有显著同源性。这些数据表明，Leu-CAMs的α亚基是通过基因复制从一个共同的祖先基因进化而来的，并强化了这样一种假说，即这些在髓样和淋巴样细胞、血小板和成纤维细胞上的异二聚体细胞黏附分子的α亚基在进化上是相关的。
