title: The Haemonchus contortus kinome--a resource for fundamental molecular investigations and drug discovery.
abstract: 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.
authors.affiliation: Faculty of Veterinary and Agricultural Sciences, The University of Melbourne, Parkville, VIC, Australia. astroehlein@unimelb.edu.au.
authors.forename: Andreas J
authors.initials: AJ
authors.lastname: Stroehlein
authors.affiliation: Faculty of Veterinary and Agricultural Sciences, The University of Melbourne, Parkville, VIC, Australia. nyoung@unimelb.edu.au.
authors.forename: Neil D
authors.initials: ND
authors.lastname: Young
authors.affiliation: Faculty of Veterinary and Agricultural Sciences, The University of Melbourne, Parkville, VIC, Australia. pasi.korhonen@unimelb.edu.au.
authors.forename: Pasi K
authors.initials: PK
authors.lastname: Korhonen
authors.affiliation: Faculty of Veterinary and Agricultural Sciences, The University of Melbourne, Parkville, VIC, Australia. jabbara@unimelb.edu.au.
authors.forename: Abdul
authors.initials: A
authors.lastname: Jabbar
authors.affiliation: Faculty of Veterinary and Agricultural Sciences, The University of Melbourne, Parkville, VIC, Australia. hofmann@griffith.edu.a.|Structural Chemistry Program, Eskitis Institute, Griffith University, Brisbane, Australia. hofmann@griffith.edu.a.
authors.forename: Andreas
authors.initials: A
authors.lastname: Hofmann
authors.affiliation: HHMI, Division of Biology, California Institute of Technology, Pasadena, CA, USA. pws@caltech.edu.
authors.forename: Paul W
authors.initials: PW
authors.lastname: Sternberg
authors.affiliation: Faculty of Veterinary and Agricultural Sciences, The University of Melbourne, Parkville, VIC, Australia. robinbg@unimelb.edu.au.
authors.forename: Robin B
authors.initials: RB
authors.lastname: Gasser
mesh_terms: D000818:Animals; D019295:Computational Biology; D016678:Genome; D006189:Haemonchus / Q000201:enzymology* / Q000235:genetics*; D011494:Protein Kinases / Q000235:genetics*; D059467:Transcriptome
chemical_list: D011494:Protein Kinases