Molecular cloning, expression, and chromosomal localization of the human earliest lymphocyte activation antigen AIM/CD69, a new member of the C-type animal lectin superfamily of signal-transmitting receptors.
Molecular cloning, expression, and chromosomal localization of the human earliest lymphocyte activation antigen AIM/CD69, a new member of the C-type animal lectin superfamily of signal-transmitting receptors.
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DOI：
10.1084/jem.178.2.537
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发表时间：
1993-08-01
期刊：
影响因子：
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通讯作者：
Sánchez-Madrid F
中科院分区：
文献类型：
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作者：
López-Cabrera M;Santis AG;Fernández-Ruiz E;Blacher R;Esch F;Sánchez-Mateos P;Sánchez-Madrid F
在体内和体外，T淋巴细胞的激活诱导CD69的表达。该分子是淋巴细胞活化过程中最早获得的可诱导细胞表面糖蛋白，参与淋巴细胞增殖，并在淋巴细胞、自然杀伤细胞和血小板中作为信号传递受体发挥作用。为了确定CD69功能的结构基础，采用基于聚合酶链式反应的策略，从纯化蛋白的多肽序列中分离出编码CD69的寡核苷酸。该基因编码597bp的CD69，编码199个氨基酸的II型膜结构蛋白，具有胞外(COOH-末端)、跨膜和胞内区。CD69克隆与1.7kb的mRNA杂交，在淋巴细胞刺激后迅速被诱导和降解，这与3‘非翻译区存在快速降解信号一致。CD69编码的多肽在COS-7细胞中的瞬时表达表明其具有与天然CD69蛋白相似的性质。通过体细胞杂交DNA分析和荧光原位杂交结合GTG显带(Giemsa胰酶G显带)，将CD69基因定位于12号染色体p13-p12。蛋白质序列同源性搜索表明，CD69是II型跨膜受体钙离子依赖(C型)凝集素超家族的新成员，包括人NKG2、大鼠NKR-P1和小鼠NKR-P1家族的NK细胞特异性基因。CD69还与其他II型凝集素细胞表面受体具有结构上的同源性，如T细胞抗原Ly49、低亲和力免疫球蛋白E受体(CD23)和肝脏去唾液酸糖蛋白受体。CD69蛋白也与这个超家族的大多数成员具有相同的功能特征，在细胞激活的早期阶段，CD69蛋白作为跨膜信号受体发挥作用。
The activation of T lymphocytes, both in vivo and in vitro, induces the expression of CD69. This molecule, which appears to be the earliest inducible cell surface glycoprotein acquired during lymphoid activation, is involved in lymphocyte proliferation and functions as a signal transmitting receptor in lymphocytes, natural killer (NK) cells, and platelets. To determine the structural basis for CD69 function, the cDNA coding for CD69 was isolated by a polymerase chain reaction-based strategy using oligonucleotides deduced from peptide sequences of the purified protein. The isolated cDNA exhibited a single open reading frame of 597 bp coding for CD69, and predicted a 199-amino acid protein of type II membrane topology, with extracellular (COOH-terminal), transmembrane, and intracellular domains. The CD69 clone hybridized to a 1.7-kb mRNA species, which was rapidly induced and degraded after lymphocyte stimulation, consistent with the presence of rapid degradation signals at the 3' untranslated region. Transient expression of the polypeptide encoded by CD69 cDNA in COS-7 cells demonstrated that it presented properties comparable to native CD69 protein. The CD69 gene was regionally mapped to chromosome 12 p13-p12 by both somatic cell hybrid DNA analysis and fluorescence in situ hybridization coupled with GTG banding (G bands by trypsin using Giemsa). Protein sequence homology search revealed that CD69 is a new member of the Ca(2+)-dependent (C-type) lectin superfamily of type II transmembrane receptors, which includes the human NKG2, the rat NKR-P1, and the mouse NKR-P1 families of NK cell-specific genes. CD69 also has a structural homology with other type II lectin cell surface receptors, such as the T cell antigen Ly49, the low avidity immunoglobulin E receptor (CD23), and the hepatic asialoglycoprotein receptors. The CD69 protein also shares functional characteristics with most members of this superfamily, which act as transmembrane signaling receptors in early phases of cellular activation.