Molecular cloning of NKp46: a novel member of the immunoglobulin superfamily involved in triggering of natural cytotoxicity.
Molecular cloning of NKp46: a novel member of the immunoglobulin superfamily involved in triggering of natural cytotoxicity.
复制标题
DOI：
10.1084/jem.188.5.953
复制
发表时间：
1998-09-07
期刊：
影响因子：
--
通讯作者：
Moretta A
中科院分区：
文献类型：
--
作者：
Pessino A;Sivori S;Bottino C;Malaspina A;Morelli L;Moretta L;Biassoni R;Moretta A
NKp46已被证明是一种新型的自然杀伤（NK）细胞特异性表面分子，参与人类NK细胞的活化。在本研究中，我们进一步分析了NKp46在针对不同肿瘤靶细胞的自然细胞毒性中的作用。我们提供了直接证据表明NKp46是一种主要的活化受体，参与对人类和鼠类肿瘤细胞的识别和裂解。尽管NKp46可能与其他活化受体（包括最近鉴定的NKp44分子）协同诱导NK介导的人类肿瘤细胞裂解，但它可能是唯一参与识别鼠类靶细胞的人类NK受体。对编码NKp46分子的cDNA进行分子克隆，发现它是免疫球蛋白（Ig）超家族的一个新成员，其细胞外部分具有两个C2型Ig样结构域。跨膜区含有带正电荷的氨基酸精氨酸（Arg），它可能参与稳定与CD3ζ链的结合。胞质部分包含30个氨基酸，不含有免疫受体酪氨酸活化基序。
对一组人/仓鼠体细胞杂种的分析显示NKp46基因在人类19号染色体上分离。对不同组织和细胞类型中NKp46 mRNA表达的评估明确证实了NKp46分子严格的NK细胞特异性。值得注意的是，与NKp46识别鼠类靶细胞上配体的能力一致，发现编码NKp46的cDNA与在鼠脾脏中表达的一种cDNA具有同源性。总之，本研究首次报道了一种在自然细胞毒性过程中参与NK细胞活化机制的NK特异性受体的分子结构特征。
NKp46 has been shown to represent a novel, natural killer (NK) cell–specific surface molecule, involved in human NK cell activation. In this study, we further analyzed the role of NKp46 in natural cytotoxicity against different tumor target cells. We provide direct evidence that NKp46 represents a major activating receptor involved in the recognition and lysis of both human and murine tumor cells. Although NKp46 may cooperate with other activating receptors (including the recently identified NKp44 molecule) in the induction of NK-mediated lysis of human tumor cells, it may represent the only human NK receptor involved in recognition of murine target cells. Molecular cloning of the cDNA encoding the NKp46 molecule revealed a novel member of the immunoglobulin (Ig) superfamily, characterized by two C2-type Ig-like domains in the extracellular portion. The transmembrane region contains the positively charged amino acid Arg, which is possibly involved in stabilizing the association with CD3ζ chain. The cytoplasmic portion, spanning 30 amino acids, does not contain immunoreceptor tyrosine-based activating motifs. Analysis of a panel of human/hamster somatic cell hybrids revealed segregation of the NKp46 gene on human chromosome 19. Assessment of the NKp46 mRNA expression in different tissues and cell types unambiguously confirmed the strict NK cell specificity of the NKp46 molecule. Remarkably, in line with the ability of NKp46 to recognize ligand(s) on murine target cells, the cDNA encoding NKp46 was found to be homologous to a cDNA expressed in murine spleen. In conclusion, this study reports the first characterization of the molecular structure of a NK-specific receptor involved in the mechanism of NK cell activation during natural cytotoxicity.
登录
查看更多内容
在人类天然杀伤细胞中，HLA-C分子的抑制（p58）和激活（p50）受体的存在。
影响因子：
15.3
作者：
Moretta, Alessandro;Sivori, Simona;Vitale, Massimo;Pende, Daniela;Morelli, Luiga;Augugliaro, Raffaella;Bottino, Cristina;Moretta, Lorenzo
通讯作者：
Moretta, Lorenzo
DOI：
10.1084/jem.183.2.645
发表时间：
1996-02-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Biassoni R;Cantoni C;Falco M;Verdiani S;Bottino C;Vitale M;Conte R;Poggi A;Moretta A;Moretta L
通讯作者：
Moretta L
DOI：
10.1084/jem.187.5.813
发表时间：
1998-03-02
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Borrego F;Ulbrecht M;Weiss EH;Coligan JE;Brooks AG
通讯作者：
Brooks AG
DOI：
10.1083/jcb.129.6.1677
发表时间：
1995-06
期刊：
The Journal of cell biology
影响因子：
--
作者：
Brakenhoff RH;Gerretsen M;Knippels EM;van Dijk M;van Essen H;Weghuis DO;Sinke RJ;Snow GB;van Dongen GA
通讯作者：
van Dongen GA
影响因子：
15.3
作者：
LITWIN, V;GUMPERZ, J;LANIER, LL
通讯作者：
LANIER, LL