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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...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2015
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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 |
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author | Stroehlein, Andreas J. Young, Neil D. Korhonen, Pasi K. Jabbar, Abdul Hofmann, Andreas Sternberg, Paul W. Gasser, Robin B. |
author_facet | Stroehlein, Andreas J. Young, Neil D. Korhonen, Pasi K. Jabbar, Abdul Hofmann, Andreas Sternberg, Paul W. Gasser, Robin B. |
author_sort | Stroehlein, Andreas J. |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-4672506 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-46725062015-12-09 The Haemonchus contortus kinome - a resource for fundamental molecular investigations and drug discovery Stroehlein, Andreas J. Young, Neil D. Korhonen, Pasi K. Jabbar, Abdul Hofmann, Andreas Sternberg, Paul W. Gasser, Robin B. Parasit Vectors Research 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. BioMed Central 2015-12-08 /pmc/articles/PMC4672506/ /pubmed/26644012 http://dx.doi.org/10.1186/s13071-015-1231-5 Text en © Stroehlein et al. 2015 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Stroehlein, Andreas J. Young, Neil D. Korhonen, Pasi K. Jabbar, Abdul Hofmann, Andreas Sternberg, Paul W. Gasser, Robin B. The Haemonchus contortus kinome - a resource for fundamental molecular investigations and drug discovery |
title | The Haemonchus contortus kinome - a resource for fundamental molecular investigations and drug discovery |
title_full | The Haemonchus contortus kinome - a resource for fundamental molecular investigations and drug discovery |
title_fullStr | The Haemonchus contortus kinome - a resource for fundamental molecular investigations and drug discovery |
title_full_unstemmed | The Haemonchus contortus kinome - a resource for fundamental molecular investigations and drug discovery |
title_short | The Haemonchus contortus kinome - a resource for fundamental molecular investigations and drug discovery |
title_sort | haemonchus contortus kinome - a resource for fundamental molecular investigations and drug discovery |
topic | Research |
url | 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 |
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