Mechanism-based small molecule probes for labeling CD38 on live cells.
Mechanism-based small molecule probes for labeling CD38 on live cells.
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DOI：
10.1021/ja808387g
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发表时间：
2009-02-11
影响因子：
15
通讯作者：
Lin H
中科院分区：
文献类型：
--
作者：
Jiang H;Congleton J;Liu Q;Merchant P;Malavasi F;Lee HC;Hao Q;Yen A;Lin H
CD38是一种具有多种功能的II型跨膜糖蛋白。它充当胞外酶和受体。酶活性催化形成两种有效的 Ca2+ 释放剂：来自烟酰胺腺嘌呤二核苷酸 (NAD) 的环腺苷二磷酸核糖 (cADPR) 和来自磷酸 NAD (NADP) 的烟酸腺嘌呤二核苷酸磷酸 (NAADP)。 CD38 的受体功能导致细胞内信号蛋白的磷酸化和免疫细胞中细胞因子产生的上调。 CD38 的这两个功能是其参与各种生物过程的基础，例如激素分泌、免疫细胞分化和免疫反应。临床上，CD38被用作慢性淋巴细胞白血病（CLL）的阴性预后标志物。然而，对于 CD38 在生理学和病理学中的作用仍然缺乏清晰的分子理解。为了促进细胞和分子水平上 CD38 的研究，我们在此报告了一种基于机制的活细胞上荧光标记 CD38 的方法。这种标记方法不会干扰CD38的受体功能和下游信号传导。因此，标记方法是研究活细胞中 CD38 受体功能的有用工具。此外，由于基于机制的标记也会抑制CD38的酶活性，因此它应该有助于剖析CD38的受体功能，而不会干扰其在复杂生物过程中的酶功能。
CD38 is a type II transmembrane glycoprotein with multiple functions. It acts as an ecto-enzyme as well as a receptor. The enzymatic activity catalyzes the formation of two potent Ca2+releasing agents: cyclic adenosine diphosphate ribose (cADPR) from nicotinamide adenine dinucleotide (NAD) and nicotinic acid adenine dinucleotide phosphate (NAADP) from NAD phosphate (NADP). The receptor function of CD38 leads to the phosphorylation of intracellular signaling proteins and the up-regulation of cytokine production in immune cells. These two functions of CD38 underlie its involvement in various biological processes, such as hormone secretion, immune cell differentiation, and immune responses. Clinically, CD38 is used as a negative prognosis marker for chronic lymphatic leukemia (CLL). However, a clear molecular understanding of CD38’s role in physiology and pathology is still lacking. To facilitate the study of CD38 at cellular and molecular levels, here we report a mechanism-based method for fluorescently labeling CD38 on live cells. This labeling method does not interfere with the receptor function of CD38 and the downstream signaling. The labeling method is thus a useful tool to study the receptor function of CD38 in live cells. In addition, since the mechanism-based labeling also inhibits the enzymatic activity of CD38, it should be useful for dissecting the receptor function of CD38 without interference from its enzyme function in complicated biological processes.
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影响因子：
48
作者：
Chen, I;Howarth, M;Ting, AY
通讯作者：
Ting, AY
影响因子：
4.3
作者：
Ausiello, CM;laSala, A;Malavasi, F
通讯作者：
Malavasi, F
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作者：
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通讯作者：
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作者：
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作者：
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通讯作者：
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