Comparative analysis of the kinomes of three pathogenic trypanosomatids: Leishmania major, Trypanosoma brucei and Trypanosoma cruzi.
Comparative analysis of the kinomes of three pathogenic trypanosomatids: Leishmania major, Trypanosoma brucei and Trypanosoma cruzi.
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三种致病性锥虫科：大型利什曼原虫、布氏锥虫和克氏锥虫的激酶组比较分析。
DOI：
10.1186/1471-2164-6-127
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发表时间：
2005-09-15
期刊：
影响因子：
4.4
通讯作者：
Mottram, JC
中科院分区：
文献类型：
--
作者：
Parsons, M;Worthey, EA;Ward, PN;Mottram, JC
大型利什曼原虫、布氏锥虫和克氏锥虫引起一些人类最衰弱的疾病：皮肤利什曼病、非洲昏睡病和恰加斯病。这些原生动物具有复杂的生命周期，涉及哺乳动物和昆虫宿主的发育，并且紧密协调的细胞周期确保高度极化细胞的繁殖。然而，寄生虫对其环境的反应和协调细胞内过程的方式知之甚少。作为努力了解寄生虫信号功能的一部分，我们报告的结果，这三个锥虫的蛋白激酶（PKs）的全基因组分析。对锥虫基因组中的真核PK（ePKs）和非典型PK（aPKs）进行生物信息学搜索，发现锥虫中共有176个PK。brucei，T. cruzi和L.主要，其中大部分是在三个物种之间的正交。这大约是人类宿主数量的30%，是疟疾寄生虫恶性疟原虫的两倍。与人类相比，各种ePK的代表性显着不同：锥虫缺乏受体连接的酪氨酸和酪氨酸激酶样激酶，尽管它们确实具有双特异性激酶。CMGC、STE和NEK集团的相对扩张已经发生。大量独特的ePKs对任何已知的基团都没有表现出很强的亲和力。锥虫具有预测的跨膜结构域的ePKs很少，这表明受体ePKs是罕见的。辅助Pfam结构域，这是经常出现在人类的ePKs，是不常见的锥虫ePKs。锥虫拥有一个大的PK集，约占每个基因组的2%，这表明磷酸化在寄生虫生物学中的关键作用。虽然可以使用生物信息学分析将大多数锥虫ePK归入7个已建立的组中，但不可能仅基于序列相似性来归属功能。因此，刺激与蛋白质磷酸化网络的联系仍然是个谜。与已知药物靶点具有显著序列相似性的许多PK的存在，以及大量可能代表新靶点的不寻常激酶的存在，强烈主张对这些分子进行功能分析。
The trypanosomatids Leishmania major, Trypanosoma brucei and Trypanosoma cruzi cause some of the most debilitating diseases of humankind: cutaneous leishmaniasis, African sleeping sickness, and Chagas disease. These protozoa possess complex life cycles that involve development in mammalian and insect hosts, and a tightly coordinated cell cycle ensures propagation of the highly polarized cells. However, the ways in which the parasites respond to their environment and coordinate intracellular processes are poorly understood. As a part of an effort to understand parasite signaling functions, we report the results of a genome-wide analysis of protein kinases (PKs) of these three trypanosomatids. Bioinformatic searches of the trypanosomatid genomes for eukaryotic PKs (ePKs) and atypical PKs (aPKs) revealed a total of 176 PKs in T. brucei, 190 in T. cruzi and 199 in L. major, most of which are orthologous across the three species. This is approximately 30% of the number in the human host and double that of the malaria parasite, Plasmodium falciparum. The representation of various groups of ePKs differs significantly as compared to humans: trypanosomatids lack receptor-linked tyrosine and tyrosine kinase-like kinases, although they do possess dual-specificity kinases. A relative expansion of the CMGC, STE and NEK groups has occurred. A large number of unique ePKs show no strong affinity to any known group. The trypanosomatids possess few ePKs with predicted transmembrane domains, suggesting that receptor ePKs are rare. Accessory Pfam domains, which are frequently present in human ePKs, are uncommon in trypanosomatid ePKs. Trypanosomatids possess a large set of PKs, comprising approximately 2% of each genome, suggesting a key role for phosphorylation in parasite biology. Whilst it was possible to place most of the trypanosomatid ePKs into the seven established groups using bioinformatic analyses, it has not been possible to ascribe function based solely on sequence similarity. Hence the connection of stimuli to protein phosphorylation networks remains enigmatic. The presence of numerous PKs with significant sequence similarity to known drug targets, as well as a large number of unusual kinases that might represent novel targets, strongly argue for functional analysis of these molecules.
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影响因子：
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