Human CD38 and CD16 are functionally dependent and physically associated in natural killer cells
Human CD38 and CD16 are functionally dependent and physically associated in natural killer cells
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DOI：
10.1182/blood.v99.7.2490
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发表时间：
2002-04-01
期刊：
影响因子：
20.3
通讯作者：
Malavasi, F
中科院分区：
文献类型：
--
作者：
Deaglio, S;Zubiaur, M;Malavasi, F
CD38是一种不受限制的表面糖蛋白，是一种调节细胞质钙的外酶（腺苷二磷酸[ADP]核糖环化酶/环ADP核糖水解酶）。该分子也作为受体，调节细胞间的相互作用并传递跨膜信号，尽管在结构上表现出缺陷。通过激动性单克隆抗体诱导CD38连接导致成人自然杀伤（NK）细胞裂解机制激活的信号类似的信号在YT和NKL， 2 CD16（-）人nk样系中不能复制。假设CD38与NK细胞表面的专业信号分子建立了功能上的合作关系。目前的工作回答了关于CD38在NK细胞中用于信号传导的分子的问题，使用CD16(-) NK细胞系作为CD16表达基因校正的模型。我们的研究结果表明，功能性CD16分子是CD38控制激活途径的必要和充分条件，该途径包括钙通量、ZAP70和丝裂原活化蛋白激酶的酪氨酸磷酸化、干扰素γ的分泌和细胞毒性反应。荧光共振能量转移和共盖实验也表明CD38和CD16表面接近。这些结果通过使用NKL细胞系得到证实，其中C16（+）和CD16（-）变体在没有遗传操作的情况下获得。总之，我们的研究结果表明CD38是一种独特的受体分子，它本身不能发出信号，但其受体功能是通过与专业信号结构的功能和物理关联来拯救的，该信号结构根据谱系和环境而变化。这个分子是NK细胞中的CD16。(C) 2002年由美国血液病学会出版。
CD38, a surface glycoprotein of unrestricted lineage, is an ectoenzyme (adenosine diphosphate [ADP] ribosyl cyclase/ cyclic ADP-ribose hydrolase) that regulates cytoplasmic calcium. The molecule also performs as a receptor, modulating cell-cell interactions and delivering transmembrane signals, despite showing a structural ineptitude to the scope. CD38 ligation by agonistic monoclonal antibodies induced signals leading to activation of the lytic machinery of natural killer (NK) cells from adults; similar signals could not be reproduced in YT and NKL, 2 CD16(-) human NK-like lines. It was hypothesized that CD38 establishes a functional cooperation with professional signaling molecules of the NK cell surface. The present work answers the question about the molecule exploited by CD38 for signaling in NK cells, using as a model CD16(-) NK lines genetically corrected for CD16 expression. Our results indicate that a functional CD16 molecule is a necessary and sufficient requisite for CD38 to control an activation pathway, which includes calcium fluxes, tyrosine phosphorylation of ZAP70 and mitogen-activated protein kinase, secretion of interferon-gamma, and cytotoxic responses. Fluorescence resonance energy transfer and cocapping experiments also showed a surface proximity between CD38 and CD16. These results were confirmed by using the NKL cell line, in which C16(+) and CD16(-) variants were obtained without genetic manipulation. Together, our findings show CD38 to be a unique receptor molecule that cannot signal by itself but whose receptor function is rescued by functional and physical associations with a professional signaling structure that varies according to lineage and environment. This molecule is CD16 in NK cells. (C) 2002 by The American Society of Hematology.