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The Haemonchus contortus kinome - a resource for fundamental molecular investigations and drug discovery

BACKGROUND: Protein kinases regulate a plethora of essential signalling and other biological pathways in all eukaryotic organisms, but very little is known about them in most parasitic nematodes. METHODS: Here, we defined, for the first time, the entire complement of protein kinases (kinome) encoded...

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Detalles Bibliográficos
Autores principales: Stroehlein, Andreas J., Young, Neil D., Korhonen, Pasi K., Jabbar, Abdul, Hofmann, Andreas, Sternberg, Paul W., Gasser, Robin B.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4672506/
https://www.ncbi.nlm.nih.gov/pubmed/26644012
http://dx.doi.org/10.1186/s13071-015-1231-5
Descripción
Sumario:BACKGROUND: Protein kinases regulate a plethora of essential signalling and other biological pathways in all eukaryotic organisms, but very little is known about them in most parasitic nematodes. METHODS: Here, we defined, for the first time, the entire complement of protein kinases (kinome) encoded in the barber’s pole worm (Haemonchus contortus) through an integrated analysis of transcriptomic and genomic datasets using an advanced bioinformatic workflow. RESULTS: We identified, curated and classified 432 kinases representing ten groups, 103 distinct families and 98 subfamilies. A comparison of the kinomes of H. contortus and Caenorhabditis elegans (a related, free-living nematode) revealed considerable variation in the numbers of casein kinases, tyrosine kinases and Ca(2+)/calmodulin-dependent protein kinases, which likely relate to differences in biology, habitat and life cycle between these worms. Moreover, a suite of kinase genes was selectively transcribed in particular developmental stages of H. contortus, indicating central roles in developmental and reproductive processes. In addition, using a ranking system, drug targets (n = 13) and associated small-molecule effectors (n = 1517) were inferred. CONCLUSIONS: The H. contortus kinome will provide a useful resource for fundamental investigations of kinases and signalling pathways in this nematode, and should assist future anthelmintic discovery efforts; this is particularly important, given current drug resistance problems in parasitic nematodes. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13071-015-1231-5) contains supplementary material, which is available to authorized users.