Plasmodium falciparum NIMA-related kinase Pfnek-1: sex specificity and assessment of essentiality for the erythrocytic asexual cycle.
Plasmodium falciparum NIMA-related kinase Pfnek-1: sex specificity and assessment of essentiality for the erythrocytic asexual cycle.
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DOI：
10.1099/mic.0.049023-0
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发表时间：
2011-10
期刊：
影响因子：
--
通讯作者：
Doerig C
中科院分区：
文献类型：
--
作者：
Dorin-Semblat D;Schmitt S;Semblat JP;Sicard A;Reininger L;Goldring D;Patterson S;Quashie N;Chakrabarti D;Meijer L;Doerig C
恶性疟原虫激酶包括与NIMA （never-in-mitosis）家族相关的四个蛋白激酶家族（Pfnek-1至-4），其成员在真核细胞的有丝分裂和减数分裂中起重要作用。其中只有Pfnek-1在无性寄生虫中表达，我们之前在生化水平上对其进行了表征。其他三个基因（Pfnek-2、-3和-4）主要在配子体中表达，并且nek-2和nek-4在减数分裂中的作用已被证实。在这里，我们通过反向遗传学证明Pfnek-1是完成红细胞无性循环所必需的，并且与Pfnek-2和Pfnek-4相比，Pfnek-1在雄性配子细胞（而不是雌性配子细胞）中的表达可以通过免疫荧光检测到。这表明Pfnek-1的功能与Pfnek家族的其他成员没有冗余，并确定Pfnek-1是抗疟疾化疗的潜在靶点。小分子文库的中等通量筛选证明了重组Pfnek-1可以作为药物发现的靶标。
The Plasmodium falciparum kinome includes a family of four protein kinases (Pfnek-1 to -4) related to the NIMA (never-in-mitosis) family, members of which play important roles in mitosis and meiosis in eukaryotic cells. Only one of these, Pfnek-1, which we previously characterized at the biochemical level, is expressed in asexual parasites. The other three (Pfnek-2, -3 and -4) are expressed predominantly in gametocytes, and a role for nek-2 and nek-4 in meiosis has been documented. Here we show by reverse genetics that Pfnek-1 is required for completion of the asexual cycle in red blood cells and that its expression in gametocytes in detectable by immunofluorescence in male (but not in female) gametocytes, in contrast with Pfnek-2 and Pfnek-4. This indicates that the function of Pfnek-1 is non-redundant with those of the other members of the Pfnek family and identifies Pfnek-1 as a potential target for antimalarial chemotherapy. A medium-throughput screen of a small-molecule library provides proof of concept that recombinant Pfnek-1 can be used as a target in drug discovery.
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影响因子：
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作者：
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通讯作者：
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作者：
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影响因子：
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作者：
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通讯作者：
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DOI：
10.1073/pnas.0802982105
发表时间：
2008-07-01
影响因子：
11.1
作者：
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通讯作者：
Winzeler, Elizabeth A.