A genomic perspective of protein kinases in Plasmodium falciparum
A genomic perspective of protein kinases in Plasmodium falciparum
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DOI：
10.1002/prot.20278
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发表时间：
2005-01-01
影响因子：
2.9
通讯作者：
Krupa, A
中科院分区：
文献类型：
--
作者：
Anamika;Srinivasan, N;Krupa, A
蛋白激酶是真核生物细胞信号传导调控的核心。以前已经从真核生物的各种完全测序的基因组中鉴定出高度保守和谱系特异性的蛋白激酶。目前的工作描述了恶性疟原虫基因组编码蛋白激酶的全基因组分析。利用几种不同的谱匹配方法，我们在寄生虫基因组中鉴定了99种蛋白激酶或相关蛋白。我们已经将这些激酶分类为亚家族，并在非催化结构域的背景下分析它们，这些非催化结构域发生在这些催化激酶结构域的蛋白质中。与大多数真核蛋白激酶相比，这些序列在长度、催化结构域插入和共发生结构域方面差异很大。催化和非催化结构域包含长链的重复带正电和其他极性氨基酸。细胞周期的各种组成部分，包括4个周期蛋白依赖性激酶（CDK）同源物，2个周期蛋白，1个CDK调节亚基和1个激酶相关磷酸酶，被确定。恶性疟原虫有丝分裂原活化蛋白激酶（MAP）激酶和MAP激酶激酶的鉴定为真核生物高度保守的信号通路提供了新的范式。钙依赖性激酶家族，在恶性疟原虫中有很好的代表，显示出与EF-hands和pleckstrin同源结构域的不同结构域组合。分析揭示了一个新的蛋白激酶亚家族，与以前已知的亚家族具有有限的序列相似性。发现了一个具有6个跨膜区域的新跨膜激酶。在其中一些蛋白激酶中发现了假定的顶质体靶向序列，表明它们输出到顶质体。(C) 2004 Wiley-Liss, Inc。
Protein kinases are central to regulation of cellular signaling in the eukaryotes. Well-conserved and lineage-specific protein kinases have previously been identified from various completely sequenced genomes of eukaryotes. The current work describes a genome-wide analysis for protein kinases encoded in the Plasmodium falciparum genome. Using a few different profile matching methods, we have identified 99 protein kinases or related proteins in the parasite genome. We have classified these kinases into subfamilies and analyzed them in the context of noncatalytic domains that occur in these catalytic kinase domain-containing proteins. Compared to most eukaryotic protein kinases, these sequences vary significantly in terms of their lengths, inserts in catalytic domains, and co-occurring domains. Catalytic and noncatalytic domains contain long stretches of repeats of positively charged and other polar amino acids. Various components of the cell cycle, including 4 cyclin-dependent kinase (CDK) homologues, 2 cyclins, 1 CDK regulatory subunit, and 1 kinase-associated phosphatase, are identified. Identification of putative mitogen-activated protein (MAP) Kinase and MAP Kinase Kinase of P. falciparum suggests a new paradigm in the highly conserved signaling pathway of eukaryotes. The calcium-dependent kinase family, well represented in P. falciparum, shows varying domain combinations with EF-hands and pleckstrin homology domains. The analysis reveals a new subfamily of protein kinases having limited sequence similarity with previously known subfamilies. A new transmembrane kinase with 6 membrane-spanning regions is identified. Putative apicoplast targeting sequences have been detected in some of these protein kinases, suggesting their export to the apicoplast. (C) 2004 Wiley-Liss, Inc.