Two novel 2-aminoethyl diphenylborinate (2-APB) analogues differentially activate and inhibit store-operated Ca(2+) entry via STIM proteins.
Two novel 2-aminoethyl diphenylborinate (2-APB) analogues differentially activate and inhibit store-operated Ca(2+) entry via STIM proteins.
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DOI：
10.1016/j.ceca.2009.10.004
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发表时间：
2010-01
期刊：
影响因子：
4
通讯作者：
Mikoshiba K
中科院分区：
文献类型：
--
作者：
Goto J;Suzuki AZ;Ozaki S;Matsumoto N;Nakamura T;Ebisui E;Fleig A;Penner R;Mikoshiba K
store - operation calcium entry （SOCE）或ICRAC（钙释放激活钙电流）是补充细胞内钙储存的重要途径，在抗原诱导的T淋巴细胞活化等细胞功能中起着不可或缺的作用。尽管ICRAC在细胞功能中的重要性，但缺乏有效和特异性的抑制剂限制了ICRAC在天然细胞中的功能。2-氨基乙基二苯硼酸盐（2-APB）是一种广泛应用的SOCE/ICRAC抑制剂，但其作用不具有特异性。在开发更有效和选择性的化合物的尝试中，我们发现了两种结构上同分异构体的2-APB类似物，其效力比2-APB本身强100倍。其中一种2-APB类似物根据浓度激活和抑制内源性SOCE，而另一种只抑制它。2-APB类似物抑制储存耗尽介导的STIM1聚集以及异源表达的CRAC电流。与2-APB不同，类似物在没有STIM的情况下不能激活CRACM3/Orai3电流，我们的研究结果表明，2-APB类似物对SOCE/ICRAC的抑制和激活是由STIM介导的。
Store-operated calcium entry (SOCE) or ICRAC (calcium release-activated calcium current) is a critical pathway to replenish intracellular calcium stores, and plays indispensable roles in cellular functions such as antigen-induced T lymphocyte activation. Despite the importance of ICRAC in cellular functions, lack of potent and specific inhibitor has limited the approaches to the function of ICRAC in native cells. 2-Aminoethyl diphenylborinate (2-APB) is a widely used SOCE/ICRAC inhibitor, while its effect is rather unspecific. In the attempt to develop more potent and selective compounds here we identified two structurally isomeric 2-APB analogues that are 100-fold more potent than 2-APB itself. One of the 2-APB analogues activates and inhibits endogenous SOCE depending on the concentration while the other only inhibits it. The 2-APB analogue inhibits store depletion-mediated STIM1 clustering as well as heterologously expressed CRAC current. Together with the observation that, unlike 2-APB, the analogue compounds failed to activate CRACM3/Orai3 current in the absence of STIM, our results suggest that inhibition and activation of SOCE/ICRAC by the 2-APB analogues is mediated by STIM.
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影响因子：
3.8
作者：
Li, Mingjiang;Jiang, Jianmin;Yue, Lixia
通讯作者：
Yue, Lixia
影响因子：
64.8
作者：
Prakriya, Murali;Feske, Stefan;Hogan, Patrick G.
通讯作者：
Hogan, Patrick G.
影响因子：
4.8
作者：
Schindl, Rainer;Bergsmann, Judith;Romanin, Christoph
通讯作者：
Romanin, Christoph
DOI：
10.1073/pnas.0608358103
发表时间：
2006-11-07
影响因子：
11.1
作者：
Baba, Yoshihiro;Hayashit, Kenji;Kurosaki, Tomohiro
通讯作者：
Kurosaki, Tomohiro
影响因子：
4
作者：
Kukkonen, JP;Lund, PE;Åkerman, KEO
通讯作者：
Åkerman, KEO