Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, Bethesda, MD 20814-4799, USA.
Exp Parasitol. 2010 Jun;125(2):156-60. doi: 10.1016/j.exppara.2010.01.012. Epub 2010 Jan 28.
cAMP-dependent protein kinases (PKAs) are central mediators of cAMP signaling in eukaryotic cells. Previously we identified a cDNA which encodes for a PKA catalytic subunit (PKA-C) in Schistosoma mansoni (SmPKA-C) that is required for adult schistosome viability in vitro. As such, SmPKA-C could potentially represent a novel schistosome chemotherapeutic target. Here we sought to identify PKA-C subunit orthologues in the other medically important schistosome species, Schistosoma haematobium and Schistosoma japonicum, to determine the degree to which this potential target is conserved and could therefore be exploited for the treatment of all forms of schistosomiasis. We report the identification of PKA-C subunit orthologues in S. haematobium and S. japonicum (ShPKA-C and SjPKA-C, respectively) and show that PKA-C orthologues are highly conserved in the Schistosoma, with over 99% amino acid sequence identity shared among the three human pathogens we examined. Furthermore, we show that the recently published Schistosoma mansoni and S. japonicum genomes contain sequences encoding for several putative PKA substrates with homology to those found in Homo sapiens, Caenorhabditis elegans, and Saccharomyces cerevisiae.
cAMP 依赖性蛋白激酶（PKA）是真核细胞中 cAMP 信号转导的核心介质。此前，我们在曼氏血吸虫（SmPKA-C）中鉴定出一种编码 PKA 催化亚基（PKA-C）的 cDNA，该亚基对于体外成体血吸虫的存活是必需的。因此，SmPKA-C 可能代表一种新的血吸虫化学治疗靶点。在这里，我们试图在其他医学上重要的血吸虫物种，埃及血吸虫和日本血吸虫中鉴定 PKA-C 亚基的同源物，以确定这个潜在的靶点在多大程度上是保守的，因此可以被利用来治疗所有形式的血吸虫病。我们报告了在埃及血吸虫和日本血吸虫中鉴定出 PKA-C 亚基的同源物（ShPKA-C 和 SjPKA-C），并表明 PKA-C 同源物在血吸虫中高度保守，我们研究的三种人类病原体之间共享超过 99%的氨基酸序列同一性。此外，我们还表明，最近发表的曼氏血吸虫和日本血吸虫基因组包含编码几种假定的 PKA 底物的序列，这些底物与在人类、秀丽隐杆线虫和酿酒酵母中发现的底物具有同源性。
