FREE SHIPPING over $40
OVER 9000 FIVE-STAR REVIEWS
5% OFF ALL SUBSCRIPTIONS
100% HAPPINESS GUARANTEE
Analyze Diet
0
Home / Equine Research Bank / Pathogens / Genome-Wide Identification and Evolutionary Analysis of Sarc...
Pathogens (Basel, Switzerland)2017; 6(1); 12; doi: 10.3390/pathogens6010012

Genome-Wide Identification and Evolutionary Analysis of Sarcocystis neurona Protein Kinases.

Abstract: The apicomplexan parasite Sarcocystis neurona causes equine protozoal myeloencephalitis (EPM), a degenerative neurological disease of horses. Due to its host range expansion, S. neurona is an emerging threat that requires close monitoring. In apicomplexans, protein kinases (PKs) have been implicated in a myriad of critical functions, such as host cell invasion, cell cycle progression and host immune response evasion. Here, we used various bioinformatics methods to define the kinome of S. neurona and phylogenetic relatedness of its PKs to other apicomplexans. We identified 97 putative PKs clustering within the various eukaryotic kinase groups. Although containing the universally-conserved PKA (AGC group), S. neurona kinome was devoid of PKB and PKC. Moreover, the kinome contains the six-conserved apicomplexan CDPKs (CAMK group). Several OPK atypical kinases, including ROPKs 19A, 27, 30, 33, 35 and 37 were identified. Notably, S. neurona is devoid of the virulence-associated ROPKs 5, 6, 18 and 38, as well as the Alpha and RIO kinases. Two out of the three S. neurona CK1 enzymes had high sequence similarities to Toxoplasma gondii TgCK1-α and TgCK1-β and the Plasmodium PfCK1. Further experimental studies on the S. neurona putative PKs identified in this study are required to validate the functional roles of the PKs and to understand their involvement in mechanisms that regulate various cellular processes and host-parasite interactions. Given the essentiality of apicomplexan PKs in the survival of apicomplexans, the current study offers a platform for future development of novel therapeutics for EPM, for instance via application of PK inhibitors to block parasite invasion and development in their host.
Get Full Text
Publication Date: 2017-03-21 PubMed ID: 28335576PubMed Central: PMC5371900DOI: 10.3390/pathogens6010012Google Scholar: Lookup
The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
LinkedInCopy
  • Journal Article

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The research paper focuses on the identification and examination of protein kinases (PKs) in the parasite Sarcocystis neurona, which causes a neurological disease in horses. These protein kinases have significant roles in the parasite’s invasiveness and development. Through the study, the researchers hope to better understand these roles and potentially develop new treatments for the disease.

Context and Motivation for the Research

  • Sarcocystis neurona is a type of parasite from the Apicomplexan group. It is the cause of a degenerative neurological disease in horses called equine protozoal myeloencephalitis (EPM).
  • The threat from this parasite is growing due to its expanding host range and as such, close monitoring of this parasite is needed.
  • In Apicomplexan parasites, protein kinases (PKs) are known to play critical roles in various functions such as host cell invasion, cell cycle progression, and evasion of host immune response.
  • The goal of this research is to identify and analyze the protein kinases present in S. neurona to understand their functions and use this information to develop potential medical treatments.

Methodology

  • Various bioinformatics methods were used to define the kinome (the complete set of protein kinases) of S. neurona and to establish their evolutionary relatedness to PKs in other apicomplexan parasites.
  • They identified 97 potential protein kinases in S. neurona, which belong to various eukaryotic kinase groups.

Key Findings

  • While the universally-conserved PKA is present in the S. neurona kinome, it did not contain PKB and PKC.
  • It did contain the six-conserved apicomplexan CDPKs, a group of calcium-regulated protein kinases.
  • Several atypical kinases, including ROPKs 19A, 27, 30, 33, 35, and 37, were identified in S. neurona.
  • Interestingly, S. neurona did not possess virulence-associated ROPKs 5, 6, 18, and 38, or Alpha and RIO kinases.
  • Two of the three S. neurona CK1 enzymes had high similarities to Toxoplasma gondii TgCK1-α and TgCK1-β and the Plasmodium PfCK1.

Conclusion and Future Work Proposals

  • Future experiments will be needed to validate the functional roles of the identified S. neurona PKs and to understand their involvement in mechanisms controlling cellular processes and host-parasite interactions.
  • Given the critical roles of protein kinases in the survival of apicomplexan parasites, this research has the potential to pave the way for the development of novel treatments for EPM, possibly through the use of PK inhibitors to block invasion and development of the parasite in its host.

Cite This Article

APA
Murungi EK, Kariithi HM. (2017). Genome-Wide Identification and Evolutionary Analysis of Sarcocystis neurona Protein Kinases. Pathogens, 6(1), 12. https://doi.org/10.3390/pathogens6010012

Publication

Pathogens (Basel, Switzerland)
ISSN: 2076-0817
NlmUniqueID: 101596317
Country: Switzerland
Language: English
Volume: 6
Issue: 1
PII: 12

Researcher Affiliations

Murungi, Edwin K
  • Department of Biochemistry and Molecular Biology, Egerton University, P.O. Box 536, 20115 Njoro, Kenya. edwin.murungi@egerton.ac.ke.
Kariithi, Henry M
  • Biotechnology Research Institute, Kenya Agricultural and Livestock Research Organization, P.O. Box 57811, Kaptagat Rd, Loresho, 00200 Nairobi, Kenya. henry.kariithi@kalro.org.

Conflict of Interest Statement

The authors declare that there is no conflict of interest in this work.

References

This article includes 92 references
  1. Dubey JP, Lindsay DS, Saville WJ, Reed SM, Granstrom DE, Speer CA. A review of Sarcocystis neurona and equine protozoal myeloencephalitis (EPM).. Vet Parasitol 2001 Feb 26;95(2-4):89-131.
    doi: 10.1016/S0304-4017(00)00384-8pubmed: 11223193google scholar: lookup
  2. Reed SM, Furr M, Howe DK, Johnson AL, MacKay RJ, Morrow JK, Pusterla N, Witonsky S. Equine Protozoal Myeloencephalitis: An Updated Consensus Statement with a Focus on Parasite Biology, Diagnosis, Treatment, and Prevention.. J Vet Intern Med 2016 Mar-Apr;30(2):491-502.
    doi: 10.1111/jvim.13834pmc: PMC4913613pubmed: 26857902google scholar: lookup
  3. Dubey JP, Howe DK, Furr M, Saville WJ, Marsh AE, Reed SM, Grigg ME. An update on Sarcocystis neurona infections in animals and equine protozoal myeloencephalitis (EPM).. Vet Parasitol 2015 Apr 15;209(1-2):1-42.
    doi: 10.1016/j.vetpar.2015.01.026pmc: PMC4461864pubmed: 25737052google scholar: lookup
  4. Howe DK, MacKay RJ, Reed SM. Equine protozoal myeloencephalitis.. Vet Clin North Am Equine Pract 2014 Dec;30(3):659-75.
    doi: 10.1016/j.cveq.2014.08.012pubmed: 25441115google scholar: lookup
  5. Colahan PT, Bailey JE, Johnson M, Rice BL, Chou CC, Cheeks JP, Jones GL, Yang M. Effect of sulfadiazine and pyrimethamine on selected physiologic and performance parameters in athletically conditioned thoroughbred horses during an incremental exercise stress test.. Vet Ther 2002 Spring;3(1):49-63.
    pubmed: 12050828
  6. McClure S.R., Palma K.G.. Treatment of equine protozoal myeloencephalitis with nitazoxanide. J. Equine Vet. Sci. 1999;19:639–641.
    doi: 10.1016/S0737-0806(06)82197-0google scholar: lookup
  7. Bernard W.V., Beech J. Neurological examination and neurological conditions causing gait deficits. In: Ross M.W., Dyson S.J., editors. Diagnosis and Management of Lameness in the Horse. 2nd ed. Elsevier Saunders; St. Louis, MO, USA: 2003. pp. 135–145.
  8. Warschauer B.A., Sondhof A.. Equine protozoal myeloencephalitis. Iowa State Univ. Vet. 1998;60:Article 10.
  9. Dubremetz JF, Garcia-Réguet N, Conseil V, Fourmaux MN. Apical organelles and host-cell invasion by Apicomplexa.. Int J Parasitol 1998 Jul;28(7):1007-13.
    doi: 10.1016/S0020-7519(98)00076-9pubmed: 9724870google scholar: lookup
  10. Sadak A, Taghy Z, Fortier B, Dubremetz JF. Characterization of a family of rhoptry proteins of Toxoplasma gondii.. Mol Biochem Parasitol 1988 Jun;29(2-3):203-11.
    doi: 10.1016/0166-6851(88)90075-8pubmed: 3045541google scholar: lookup
  11. Cesbron-Delauw MF, Gendrin C, Travier L, Ruffiot P, Mercier C. Apicomplexa in mammalian cells: trafficking to the parasitophorous vacuole.. Traffic 2008 May;9(5):657-64.
    doi: 10.1111/j.1600-0854.2008.00728.xpubmed: 18315533google scholar: lookup
  12. Hanks SK, Hunter T. Protein kinases 6. The eukaryotic protein kinase superfamily: kinase (catalytic) domain structure and classification.. FASEB J 1995 May;9(8):576-96.
    pubmed: 7768349
  13. Manning G, Whyte DB, Martinez R, Hunter T, Sudarsanam S. The protein kinase complement of the human genome.. Science 2002 Dec 6;298(5600):1912-34.
    doi: 10.1126/science.1075762pubmed: 12471243google scholar: lookup
  14. Manning G, Plowman GD, Hunter T, Sudarsanam S. Evolution of protein kinase signaling from yeast to man.. Trends Biochem Sci 2002 Oct;27(10):514-20.
    doi: 10.1016/S0968-0004(02)02179-5pubmed: 12368087google scholar: lookup
  15. Hanks SK, Quinn AM, Hunter T. The protein kinase family: conserved features and deduced phylogeny of the catalytic domains.. Science 1988 Jul 1;241(4861):42-52.
    doi: 10.1126/science.3291115pubmed: 3291115google scholar: lookup
  16. Miranda-Saavedra D, Barton GJ. Classification and functional annotation of eukaryotic protein kinases.. Proteins 2007 Sep 1;68(4):893-914.
    doi: 10.1002/prot.21444pubmed: 17557329google scholar: lookup
  17. Miranda-Saavedra D, Gabaldón T, Barton GJ, Langsley G, Doerig C. The kinomes of apicomplexan parasites.. Microbes Infect 2012 Aug;14(10):796-810.
    doi: 10.1016/j.micinf.2012.04.007pubmed: 22587893google scholar: lookup
  18. Ward P, Equinet L, Packer J, Doerig C. Protein kinases of the human malaria parasite Plasmodium falciparum: the kinome of a divergent eukaryote.. BMC Genomics 2004 Oct 12;5:79.
    doi: 10.1186/1471-2164-5-79pmc: PMC526369pubmed: 15479470google scholar: lookup
  19. Anamika, Srinivasan N, Krupa A. A genomic perspective of protein kinases in Plasmodium falciparum.. Proteins 2005 Jan 1;58(1):180-9.
    pubmed: 15515182doi: 10.1002/prot.20278google scholar: lookup
  20. Talevich E, Tobin AB, Kannan N, Doerig C. An evolutionary perspective on the kinome of malaria parasites.. Philos Trans R Soc Lond B Biol Sci 2012 Sep 19;367(1602):2607-18.
    doi: 10.1098/rstb.2012.0014pmc: PMC3415840pubmed: 22889911google scholar: lookup
  21. Tewari R, Straschil U, Bateman A, Böhme U, Cherevach I, Gong P, Pain A, Billker O. The systematic functional analysis of Plasmodium protein kinases identifies essential regulators of mosquito transmission.. Cell Host Microbe 2010 Oct 21;8(4):377-87.
    doi: 10.1016/j.chom.2010.09.006pmc: PMC2977076pubmed: 20951971google scholar: lookup
  22. Talevich E, Mirza A, Kannan N. Structural and evolutionary divergence of eukaryotic protein kinases in Apicomplexa.. BMC Evol Biol 2011 Nov 2;11:321.
    doi: 10.1186/1471-2148-11-321pmc: PMC3239843pubmed: 22047078google scholar: lookup
  23. Talevich E, Kannan N. Structural and evolutionary adaptation of rhoptry kinases and pseudokinases, a family of coccidian virulence factors.. BMC Evol Biol 2013 Jun 6;13:117.
    doi: 10.1186/1471-2148-13-117pmc: PMC3682881pubmed: 23742205google scholar: lookup
  24. Talevich E., Kannan N., Miranda-Saavedra D.. Computational analysis of apicomplexan kinomes. 2014. pp. 1–36.
  25. Kumar A, Vaid A, Syin C, Sharma P. PfPKB, a novel protein kinase B-like enzyme from Plasmodium falciparum: I. Identification, characterization, and possible role in parasite development.. J Biol Chem 2004 Jun 4;279(23):24255-64.
    doi: 10.1074/jbc.M312855200pubmed: 15024016google scholar: lookup
  26. Billker O, Lourido S, Sibley LD. Calcium-dependent signaling and kinases in apicomplexan parasites.. Cell Host Microbe 2009 Jun 18;5(6):612-22.
    doi: 10.1016/j.chom.2009.05.017pmc: PMC2718762pubmed: 19527888google scholar: lookup
  27. Abdi A, Eschenlauer S, Reininger L, Doerig C. SAM domain-dependent activity of PfTKL3, an essential tyrosine kinase-like kinase of the human malaria parasite Plasmodium falciparum.. Cell Mol Life Sci 2010 Oct;67(19):3355-69.
    doi: 10.1007/s00018-010-0434-3pmc: PMC2933843pubmed: 20582613google scholar: lookup
  28. Wang Z, Wang S, Wang W, Gu Y, Liu H, Wei F, Liu Q. Targeted disruption of CK1α in Toxoplasma gondii increases acute virulence in mice.. Eur J Protistol 2016 Oct;56:90-101.
    doi: 10.1016/j.ejop.2016.07.006pubmed: 27567091google scholar: lookup
  29. Agarwal S, Kern S, Halbert J, Przyborski JM, Baumeister S, Dandekar T, Doerig C, Pradel G. Two nucleus-localized CDK-like kinases with crucial roles for malaria parasite erythrocytic replication are involved in phosphorylation of splicing factor.. J Cell Biochem 2011 May;112(5):1295-310.
    doi: 10.1002/jcb.23034pubmed: 21312235google scholar: lookup
  30. Andrade LF, Nahum LA, Avelar LG, Silva LL, Zerlotini A, Ruiz JC, Oliveira G. Eukaryotic protein kinases (ePKs) of the helminth parasite Schistosoma mansoni.. BMC Genomics 2011 May 6;12:215.
    doi: 10.1186/1471-2164-12-215pmc: PMC3117856pubmed: 21548963google scholar: lookup
  31. Low H, Lye YM, Sim TS. Pfnek3 functions as an atypical MAPKK in Plasmodium falciparum.. Biochem Biophys Res Commun 2007 Sep 21;361(2):439-44.
    doi: 10.1016/j.bbrc.2007.07.047pubmed: 17662247google scholar: lookup
  32. Dorin D, Le Roch K, Sallicandro P, Alano P, Parzy D, Poullet P, Meijer L, Doerig C. Pfnek-1, a NIMA-related kinase from the human malaria parasite Plasmodium falciparum Biochemical properties and possible involvement in MAPK regulation.. Eur J Biochem 2001 May;268(9):2600-8.
    doi: 10.1046/j.1432-1327.2001.02151.xpubmed: 11322879google scholar: lookup
  33. Berry L, Chen CT, Reininger L, Carvalho TG, El Hajj H, Morlon-Guyot J, Bordat Y, Lebrun M, Gubbels MJ, Doerig C, Daher W. The conserved apicomplexan Aurora kinase TgArk3 is involved in endodyogeny, duplication rate and parasite virulence.. Cell Microbiol 2016 Aug;18(8):1106-1120.
    doi: 10.1111/cmi.12571pmc: PMC4961599pubmed: 26833682google scholar: lookup
  34. Sullivan WJ Jr, Narasimhan J, Bhatti MM, Wek RC. Parasite-specific eIF2 (eukaryotic initiation factor-2) kinase required for stress-induced translation control.. Biochem J 2004 Jun 1;380(Pt 2):523-31.
    doi: 10.1042/bj20040262pmc: PMC1224182pubmed: 14989696google scholar: lookup
  35. Blazejewski T, Nursimulu N, Pszenny V, Dangoudoubiyam S, Namasivayam S, Chiasson MA, Chessman K, Tonkin M, Swapna LS, Hung SS, Bridgers J, Ricklefs SM, Boulanger MJ, Dubey JP, Porcella SF, Kissinger JC, Howe DK, Grigg ME, Parkinson J. Systems-based analysis of the Sarcocystis neurona genome identifies pathways that contribute to a heteroxenous life cycle.. mBio 2015 Feb 10;6(1).
    doi: 10.1128/mBio.02445-14pmc: PMC4337577pubmed: 25670772google scholar: lookup
  36. Dice JF, Goldberg AL. Relationship between in vivo degradative rates and isoelectric points of proteins.. Proc Natl Acad Sci U S A 1975 Oct;72(10):3893-7.
    doi: 10.1073/pnas.72.10.3893pmc: PMC433102pubmed: 1060070google scholar: lookup
  37. Conesa A, Götz S, García-Gómez JM, Terol J, Talón M, Robles M. Blast2GO: a universal tool for annotation, visualization and analysis in functional genomics research.. Bioinformatics 2005 Sep 15;21(18):3674-6.
    doi: 10.1093/bioinformatics/bti610pubmed: 16081474google scholar: lookup
  38. Kato K, Sugi T, Takemae H, Takano R, Gong H, Ishiwa A, Horimoto T, Akashi H. Characterization of a Toxoplasma gondii calcium calmodulin-dependent protein kinase homolog.. Parasit Vectors 2016 Jul 21;9(1):405.
    doi: 10.1186/s13071-016-1676-1pmc: PMC4957278pubmed: 27444499google scholar: lookup
  39. Khan F, Tang J, Qin CL, Kim K. Cyclin-dependent kinase TPK2 is a critical cell cycle regulator in Toxoplasma gondii.. Mol Microbiol 2002 Jul;45(2):321-32.
    doi: 10.1046/j.1365-2958.2002.03026.xpubmed: 12123447google scholar: lookup
  40. Solyakov L, Halbert J, Alam MM, Semblat JP, Dorin-Semblat D, Reininger L, Bottrill AR, Mistry S, Abdi A, Fennell C, Holland Z, Demarta C, Bouza Y, Sicard A, Nivez MP, Eschenlauer S, Lama T, Thomas DC, Sharma P, Agarwal S, Kern S, Pradel G, Graciotti M, Tobin AB, Doerig C. Global kinomic and phospho-proteomic analyses of the human malaria parasite Plasmodium falciparum.. Nat Commun 2011 Nov 29;2:565.
    doi: 10.1038/ncomms1558pubmed: 22127061google scholar: lookup
  41. Gurnett AM, Liberator PA, Dulski PM, Salowe SP, Donald RG, Anderson JW, Wiltsie J, Diaz CA, Harris G, Chang B, Darkin-Rattray SJ, Nare B, Crumley T, Blum PS, Misura AS, Tamas T, Sardana MK, Yuan J, Biftu T, Schmatz DM. Purification and molecular characterization of cGMP-dependent protein kinase from Apicomplexan parasites. A novel chemotherapeutic target.. J Biol Chem 2002 May 3;277(18):15913-22.
    doi: 10.1074/jbc.M108393200pubmed: 11834729google scholar: lookup
  42. Kissinger JC, Gajria B, Li L, Paulsen IT, Roos DS. ToxoDB: accessing the Toxoplasma gondii genome.. Nucleic Acids Res 2003 Jan 1;31(1):234-6.
    doi: 10.1093/nar/gkg072pmc: PMC165519pubmed: 12519989google scholar: lookup
  43. Lourido S, Shuman J, Zhang C, Shokat KM, Hui R, Sibley LD. Calcium-dependent protein kinase 1 is an essential regulator of exocytosis in Toxoplasma.. Nature 2010 May 20;465(7296):359-62.
    doi: 10.1038/nature09022pmc: PMC2874977pubmed: 20485436google scholar: lookup
  44. Donald RG, Zhong T, Meijer L, Liberator PA. Characterization of two T. gondii CK1 isoforms.. Mol Biochem Parasitol 2005 May;141(1):15-27.
    doi: 10.1016/j.molbiopara.2005.01.011pubmed: 15811523google scholar: lookup
  45. Dorin-Semblat D, Demarta-Gatsi C, Hamelin R, Armand F, Carvalho TG, Moniatte M, Doerig C. Malaria Parasite-Infected Erythrocytes Secrete PfCK1, the Plasmodium Homologue of the Pleiotropic Protein Kinase Casein Kinase 1.. PLoS One 2015;10(12):e0139591.
    doi: 10.1371/journal.pone.0139591pmc: PMC4668060pubmed: 26629826google scholar: lookup
  46. Masch A, Kunick C. Selective inhibitors of Plasmodium falciparum glycogen synthase-3 (PfGSK-3): New antimalarial agents?. Biochim Biophys Acta 2015 Oct;1854(10 Pt B):1644-9.
    doi: 10.1016/j.bbapap.2015.03.013pubmed: 25861860google scholar: lookup
  47. Peixoto L, Chen F, Harb OS, Davis PH, Beiting DP, Brownback CS, Ouloguem D, Roos DS. Integrative genomic approaches highlight a family of parasite-specific kinases that regulate host responses.. Cell Host Microbe 2010 Aug 19;8(2):208-18.
    doi: 10.1016/j.chom.2010.07.004pmc: PMC2963626pubmed: 20709297google scholar: lookup
  48. Sibley LD, Qiu W, Fentress S, Taylor SJ, Khan A, Hui R. Forward genetics in Toxoplasma gondii reveals a family of rhoptry kinases that mediates pathogenesis.. Eukaryot Cell 2009 Aug;8(8):1085-93.
    doi: 10.1128/EC.00107-09pmc: PMC2725553pubmed: 19465561google scholar: lookup
  49. Erdmann M, Scholz A, Melzer IM, Schmetz C, Wiese M. Interacting protein kinases involved in the regulation of flagellar length.. Mol Biol Cell 2006 Apr;17(4):2035-45.
    doi: 10.1091/mbc.E05-10-0976pmc: PMC1415332pubmed: 16467378google scholar: lookup
  50. Köhler S. Multi-membrane-bound structures of Apicomplexa: II. the ovoid mitochondrial cytoplasmic (OMC) complex of Toxoplasma gondii tachyzoites.. Parasitol Res 2006 Mar;98(4):355-69.
    doi: 10.1007/s00436-005-0066-ypubmed: 16470415google scholar: lookup
  51. Artz JD, Wernimont AK, Allali-Hassani A, Zhao Y, Amani M, Lin YH, Senisterra G, Wasney GA, Fedorov O, King O, Roos A, Lunin VV, Qiu W, Finerty P Jr, Hutchinson A, Chau I, von Delft F, MacKenzie F, Lew J, Kozieradzki I, Vedadi M, Schapira M, Zhang C, Shokat K, Heightman T, Hui R. The Cryptosporidium parvum kinome.. BMC Genomics 2011 Sep 30;12:478.
    doi: 10.1186/1471-2164-12-478pmc: PMC3227725pubmed: 21962082google scholar: lookup
  52. Alam MM, Solyakov L, Bottrill AR, Flueck C, Siddiqui FA, Singh S, Mistry S, Viskaduraki M, Lee K, Hopp CS, Chitnis CE, Doerig C, Moon RW, Green JL, Holder AA, Baker DA, Tobin AB. Phosphoproteomics reveals malaria parasite Protein Kinase G as a signalling hub regulating egress and invasion.. Nat Commun 2015 Jul 7;6:7285.
    doi: 10.1038/ncomms8285pmc: PMC4507021pubmed: 26149123google scholar: lookup
  53. Pearce LR, Komander D, Alessi DR. The nuts and bolts of AGC protein kinases.. Nat Rev Mol Cell Biol 2010 Jan;11(1):9-22.
    doi: 10.1038/nrm2822pubmed: 20027184google scholar: lookup
  54. Morlon-Guyot J, Berry L, Chen CT, Gubbels MJ, Lebrun M, Daher W. The Toxoplasma gondii calcium-dependent protein kinase 7 is involved in early steps of parasite division and is crucial for parasite survival.. Cell Microbiol 2014 Jan;16(1):95-114.
    doi: 10.1111/cmi.12186pmc: PMC4091637pubmed: 24011186google scholar: lookup
  55. Iwanaga T, Sugi T, Kobayashi K, Takemae H, Gong H, Ishiwa A, Murakoshi F, Recuenco FC, Horimoto T, Akashi H, Kato K. Characterization of Plasmodium falciparum cdc2-related kinase and the effects of a CDK inhibitor on the parasites in erythrocytic schizogony.. Parasitol Int 2013 Oct;62(5):423-30.
    doi: 10.1016/j.parint.2013.05.003pubmed: 23688804google scholar: lookup
  56. Aubol BE, Adams JA. Recruiting a silent partner for activation of the protein kinase SRPK1.. Biochemistry 2014 Jul 22;53(28):4625-34.
    doi: 10.1021/bi500483mpmc: PMC4108178pubmed: 24984036google scholar: lookup
  57. Eckert D, Andrée N, Razanau A, Zock-Emmenthal S, Lützelberger M, Plath S, Schmidt H, Guerra-Moreno A, Cozzuto L, Ayté J, Käufer NF. Prp4 Kinase Grants the License to Splice: Control of Weak Splice Sites during Spliceosome Activation.. PLoS Genet 2016 Jan;12(1):e1005768.
    doi: 10.1371/journal.pgen.1005768pmc: PMC4701394pubmed: 26730850google scholar: lookup
  58. Gazarini ML, Garcia CR. Interruption of the blood-stage cycle of the malaria parasite, Plasmodium chabaudi, by protein tyrosine kinase inhibitors.. Braz J Med Biol Res 2003 Nov;36(11):1465-9.
    doi: 10.1590/S0100-879X2003001100003pubmed: 14576900google scholar: lookup
  59. Kern S, Agarwal S, Huber K, Gehring AP, Strödke B, Wirth CC, Brügl T, Abodo LO, Dandekar T, Doerig C, Fischer R, Tobin AB, Alam MM, Bracher F, Pradel G. Inhibition of the SR protein-phosphorylating CLK kinases of Plasmodium falciparum impairs blood stage replication and malaria transmission.. PLoS One 2014;9(9):e105732.
    doi: 10.1371/journal.pone.0105732pmc: PMC4154858pubmed: 25188378google scholar: lookup
  60. Rüben K, Wurzlbauer A, Walte A, Sippl W, Bracher F, Becker W. Selectivity Profiling and Biological Activity of Novel β-Carbolines as Potent and Selective DYRK1 Kinase Inhibitors.. PLoS One 2015;10(7):e0132453.
    doi: 10.1371/journal.pone.0132453pmc: PMC4508061pubmed: 26192590google scholar: lookup
  61. Brumlik MJ, Pandeswara S, Ludwig SM, Murthy K, Curiel TJ. Parasite mitogen-activated protein kinases as drug discovery targets to treat human protozoan pathogens.. J Signal Transduct 2011;2011:971968.
    doi: 10.1155/2011/971968pmc: PMC3100106pubmed: 21637385google scholar: lookup
  62. Brumlik MJ, Pandeswara S, Ludwig SM, Jeansonne DP, Lacey MR, Murthy K, Daniel BJ, Wang RF, Thibodeaux SR, Church KM, Hurez V, Kious MJ, Zhang B, Alagbala A, Xia X, Curiel TJ. TgMAPK1 is a Toxoplasma gondii MAP kinase that hijacks host MKK3 signals to regulate virulence and interferon-γ-mediated nitric oxide production.. Exp Parasitol 2013 Jul;134(3):389-99.
    doi: 10.1016/j.exppara.2013.03.016pmc: PMC4226171pubmed: 23541881google scholar: lookup
  63. Fox BA, Rommereim LM, Guevara RB, Falla A, Hortua Triana MA, Sun Y, Bzik DJ. The Toxoplasma gondii Rhoptry Kinome Is Essential for Chronic Infection.. mBio 2016 May 10;7(3).
    doi: 10.1128/mBio.00193-16pmc: PMC4959664pubmed: 27165797google scholar: lookup
  64. Lawrence JG, Hendrix RW, Casjens S. Where are the pseudogenes in bacterial genomes?. Trends Microbiol 2001 Nov;9(11):535-40.
    doi: 10.1016/S0966-842X(01)02198-9pubmed: 11825713google scholar: lookup
  65. Templeton TJ, Iyer LM, Anantharaman V, Enomoto S, Abrahante JE, Subramanian GM, Hoffman SL, Abrahamsen MS, Aravind L. Comparative analysis of apicomplexa and genomic diversity in eukaryotes.. Genome Res 2004 Sep;14(9):1686-95.
    doi: 10.1101/gr.2615304pmc: PMC515313pubmed: 15342554google scholar: lookup
  66. Sugi T, Ma YF, Tomita T, Murakoshi F, Eaton MS, Yakubu R, Han B, Tu V, Kato K, Kawazu S, Gupta N, Suvorova ES, White MW, Kim K, Weiss LM. Toxoplasma gondii Cyclic AMP-Dependent Protein Kinase Subunit 3 Is Involved in the Switch from Tachyzoite to Bradyzoite Development.. mBio 2016 May 31;7(3).
    doi: 10.1128/mBio.00755-16pmc: PMC4895117pubmed: 27247232google scholar: lookup
  67. Gaji RY, Johnson DE, Treeck M, Wang M, Hudmon A, Arrizabalaga G. Phosphorylation of a Myosin Motor by TgCDPK3 Facilitates Rapid Initiation of Motility during Toxoplasma gondii egress.. PLoS Pathog 2015;11(11):e1005268.
    doi: 10.1371/journal.ppat.1005268pmc: PMC4636360pubmed: 26544049google scholar: lookup
  68. Long S, Wang Q, Sibley LD. Analysis of Noncanonical Calcium-Dependent Protein Kinases in Toxoplasma gondii by Targeted Gene Deletion Using CRISPR/Cas9.. Infect Immun 2016 May;84(5):1262-1273.
    doi: 10.1128/IAI.01173-15pmc: PMC4862710pubmed: 26755159google scholar: lookup
  69. Ojo KK, Larson ET, Keyloun KR, Castaneda LJ, Derocher AE, Inampudi KK, Kim JE, Arakaki TL, Murphy RC, Zhang L, Napuli AJ, Maly DJ, Verlinde CL, Buckner FS, Parsons M, Hol WG, Merritt EA, Van Voorhis WC. Toxoplasma gondii calcium-dependent protein kinase 1 is a target for selective kinase inhibitors.. Nat Struct Mol Biol 2010 May;17(5):602-7.
    doi: 10.1038/nsmb.1818pmc: PMC2896873pubmed: 20436472google scholar: lookup
  70. Malumbres M, Barbacid M. Cell cycle, CDKs and cancer: a changing paradigm.. Nat Rev Cancer 2009 Mar;9(3):153-66.
    doi: 10.1038/nrc2602pubmed: 19238148google scholar: lookup
  71. Cao L, Wang Z, Wang S, Li J, Wang X, Wei F, Liu Q. Deletion of mitogen-activated protein kinase 1 inhibits development and growth of Toxoplasma gondii.. Parasitol Res 2016 Feb;115(2):797-805.
    doi: 10.1007/s00436-015-4807-2pubmed: 26526952google scholar: lookup
  72. Li ZY, Wang ZD, Huang SY, Zhu XQ, Liu Q. TgERK7 is involved in the intracellular proliferation of Toxoplasma gondii.. Parasitol Res 2016 Sep;115(9):3419-24.
    doi: 10.1007/s00436-016-5103-5pubmed: 27150970google scholar: lookup
  73. Behnke MS, Fentress SJ, Mashayekhi M, Li LX, Taylor GA, Sibley LD. The polymorphic pseudokinase ROP5 controls virulence in Toxoplasma gondii by regulating the active kinase ROP18.. PLoS Pathog 2012;8(11):e1002992.
    doi: 10.1371/journal.ppat.1002992pmc: PMC3493473pubmed: 23144612google scholar: lookup
  74. Jones NG, Wang Q, Sibley LD. Secreted protein kinases regulate cyst burden during chronic toxoplasmosis.. Cell Microbiol 2017 Feb;19(2).
    doi: 10.1111/cmi.12651pmc: PMC5241228pubmed: 27450947google scholar: lookup
  75. Knoll LJ. Functional Analysis of the Rhoptry Kinome during Chronic Toxoplasma gondii Infection.. mBio 2016 Jun 14;7(3).
    doi: 10.1128/mBio.00842-16pmc: PMC4916387pubmed: 27302762google scholar: lookup
  76. Doerig C. Protein kinases as targets for anti-parasitic chemotherapy.. Biochim Biophys Acta 2004 Mar 11;1697(1-2):155-68.
    doi: 10.1016/j.bbapap.2003.11.021pubmed: 15023358google scholar: lookup
  77. Zhang VM, Chavchich M, Waters NC. Targeting protein kinases in the malaria parasite: update of an antimalarial drug target.. Curr Top Med Chem 2012;12(5):456-72.
    doi: 10.2174/156802612799362922pubmed: 22242850google scholar: lookup
  78. Cohen P. The regulation of protein function by multisite phosphorylation--a 25 year update.. Trends Biochem Sci 2000 Dec;25(12):596-601.
    doi: 10.1016/S0968-0004(00)01712-6pubmed: 11116185google scholar: lookup
  79. Eglen RM, Reisine T. The current status of drug discovery against the human kinome.. Assay Drug Dev Technol 2009 Feb;7(1):22-43.
    doi: 10.1089/adt.2008.164pubmed: 19382888google scholar: lookup
  80. Ojo KK, Dangoudoubiyam S, Verma SK, Scheele S, DeRocher AE, Yeargan M, Choi R, Smith TR, Rivas KL, Hulverson MA, Barrett LK, Fan E, Maly DJ, Parsons M, Dubey JP, Howe DK, Van Voorhis WC. Selective inhibition of Sarcocystis neurona calcium-dependent protein kinase 1 for equine protozoal myeloencephalitis therapy.. Int J Parasitol 2016 Dec;46(13-14):871-880.
    doi: 10.1016/j.ijpara.2016.08.003pmc: PMC5130624pubmed: 27729271google scholar: lookup
  81. Dissous C, Grevelding CG. Piggy-backing the concept of cancer drugs for schistosomiasis treatment: a tangible perspective?. Trends Parasitol 2011 Feb;27(2):59-66.
    doi: 10.1016/j.pt.2010.09.001pubmed: 20920890google scholar: lookup
  82. Martin DM, Miranda-Saavedra D, Barton GJ. Kinomer v. 1.0: a database of systematically classified eukaryotic protein kinases.. Nucleic Acids Res 2009 Jan;37(Database issue):D244-50.
    doi: 10.1093/nar/gkn834pmc: PMC2686601pubmed: 18974176google scholar: lookup
  83. Eddy SR. Profile hidden Markov models.. Bioinformatics 1998;14(9):755-63.
    doi: 10.1093/bioinformatics/14.9.755pubmed: 9918945google scholar: lookup
  84. Sundarsanam S., Bingham J., Manning G., Charydczak G., Chen M.J.. Kinase.com—Genomics, Evolution and Function of Protein Kinases. 1999.
  85. Gasteiger E., Hoogland C., Gattiker A., Duvaud S., Wilkins M.R., Appel R.D., Bairoch A.. Protein identification and analysis tools on the ExPASy server. 2005. pp. 571–607.
  86. Bailey TL, Boden M, Buske FA, Frith M, Grant CE, Clementi L, Ren J, Li WW, Noble WS. MEME SUITE: tools for motif discovery and searching.. Nucleic Acids Res 2009 Jul;37(Web Server issue):W202-8.
    doi: 10.1093/nar/gkp335pmc: PMC2703892pubmed: 19458158google scholar: lookup
  87. Edgar RC. MUSCLE: multiple sequence alignment with high accuracy and high throughput.. Nucleic Acids Res 2004;32(5):1792-7.
    doi: 10.1093/nar/gkh340pmc: PMC390337pubmed: 15034147google scholar: lookup
  88. Waterhouse AM, Procter JB, Martin DM, Clamp M, Barton GJ. Jalview Version 2--a multiple sequence alignment editor and analysis workbench.. Bioinformatics 2009 May 1;25(9):1189-91.
    doi: 10.1093/bioinformatics/btp033pmc: PMC2672624pubmed: 19151095google scholar: lookup
  89. Guindon S, Dufayard JF, Lefort V, Anisimova M, Hordijk W, Gascuel O. New algorithms and methods to estimate maximum-likelihood phylogenies: assessing the performance of PhyML 3.0.. Syst Biol 2010 May;59(3):307-21.
    doi: 10.1093/sysbio/syq010pubmed: 20525638google scholar: lookup
  90. Stamatakis A. RAxML version 8: a tool for phylogenetic analysis and post-analysis of large phylogenies.. Bioinformatics 2014 May 1;30(9):1312-3.
    doi: 10.1093/bioinformatics/btu033pmc: PMC3998144pubmed: 24451623google scholar: lookup
  91. Ronquist F, Teslenko M, van der Mark P, Ayres DL, Darling A, Höhna S, Larget B, Liu L, Suchard MA, Huelsenbeck JP. MrBayes 3.2: efficient Bayesian phylogenetic inference and model choice across a large model space.. Syst Biol 2012 May;61(3):539-42.
    doi: 10.1093/sysbio/sys029pmc: PMC3329765pubmed: 22357727google scholar: lookup
  92. Letunic I, Bork P. Interactive tree of life (iTOL) v3: an online tool for the display and annotation of phylogenetic and other trees.. Nucleic Acids Res 2016 Jul 8;44(W1):W242-5.
    doi: 10.1093/nar/gkw290pmc: PMC4987883pubmed: 27095192google scholar: lookup

Citations

This article has been cited 2 times.
  1. Hammarton TC. Who Needs a Contractile Actomyosin Ring? The Plethora of Alternative Ways to Divide a Protozoan Parasite.. Front Cell Infect Microbiol 2019;9:397.
    doi: 10.3389/fcimb.2019.00397pubmed: 31824870google scholar: lookup
  2. Bowden GD, Land KM, O'Connor RM, Fritz HM. High-throughput screen of drug repurposing library identifies inhibitors of Sarcocystis neurona growth.. Int J Parasitol Drugs Drug Resist 2018 Apr;8(1):137-144.
    doi: 10.1016/j.ijpddr.2018.02.002pubmed: 29547840google scholar: lookup
Subscribe to our newsletter
Join 99,344 horse owners like you who receive our email updates on horse health and nutrition.