title: Regulation of Schistosoma mansoni development and reproduction by the mitogen-activated protein kinase signaling pathway.
abstract: BACKGROUND
  Protein kinases are proven targets for drug development with an increasing number of eukaryotic Protein Kinase (ePK) inhibitors now approved as drugs. Mitogen-activated protein kinase (MAPK) family members connect cell-surface receptors to regulatory targets within cells and influence a number of tissue-specific biological activities such as cell proliferation, differentiation and survival. However, the contributions of members of the MAPK pathway to schistosome development and survival are unclear.
  
  
  RESULTS
  We employed RNA interference (RNAi) to elucidate the functional roles of five S. mansoni genes (SmCaMK2, SmJNK, SmERK1, SmERK2 and SmRas) involved in MAPK signaling pathway. Mice were injected with post-infective larvae (schistosomula) subsequent to RNAi and the development of adult worms observed. The data demonstrate that SmJNK participates in parasite maturation and survival of the parasites, whereas SmERK are involved in egg production as infected mice had significantly lower egg burdens with female worms presenting underdeveloped ovaries. Furthermore, it was shown that the c-fos transcription factor was overexpressed in parasites submitted to RNAi of SmERK1, SmJNK and SmCaMK2 indicating its putative involvement in gene regulation in this parasite's MAPK signaling cascade.
  
  
  CONCLUSIONS
  We conclude that MAPKs proteins play important roles in the parasite in vivo survival, being essential for normal development and successful survival and reproduction of the schistosome parasite. Moreover SmERK and SmJNK are potential targets for drug development.
authors.affiliation: Grupo de Genômica e Biologia Computacional, Instituto Nacional de Ciência e Tecnologia em Doenças Tropicais and Centro de Excelência em Bioinformática- CEBio, Centro de Pesquisas René Rachou, Fundação Oswaldo Cruz - FIOCRUZ, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Luiza Freire de
authors.initials: LF
authors.lastname: Andrade
authors.affiliation: Grupo de Genômica e Biologia Computacional, Instituto Nacional de Ciência e Tecnologia em Doenças Tropicais and Centro de Excelência em Bioinformática- CEBio, Centro de Pesquisas René Rachou, Fundação Oswaldo Cruz - FIOCRUZ, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Marina de Moraes
authors.initials: Mde M
authors.lastname: Mourão
authors.affiliation: Grupo de Genômica e Biologia Computacional, Instituto Nacional de Ciência e Tecnologia em Doenças Tropicais and Centro de Excelência em Bioinformática- CEBio, Centro de Pesquisas René Rachou, Fundação Oswaldo Cruz - FIOCRUZ, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Juliana Assis
authors.initials: JA
authors.lastname: Geraldo
authors.affiliation: Grupo de Genômica e Biologia Computacional, Instituto Nacional de Ciência e Tecnologia em Doenças Tropicais and Centro de Excelência em Bioinformática- CEBio, Centro de Pesquisas René Rachou, Fundação Oswaldo Cruz - FIOCRUZ, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Fernanda Sales
authors.initials: FS
authors.lastname: Coelho
authors.affiliation: Grupo de Genômica e Biologia Computacional, Instituto Nacional de Ciência e Tecnologia em Doenças Tropicais and Centro de Excelência em Bioinformática- CEBio, Centro de Pesquisas René Rachou, Fundação Oswaldo Cruz - FIOCRUZ, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Larissa Lopes
authors.initials: LL
authors.lastname: Silva
authors.affiliation: Biologia Parasitária, Departamento de Ensino, Pavilhão Arthur Neiva, Instituto Oswaldo Cruz, Fiocruz, Rio de Janeiro, Rio de Janeiro, Brazil; Laboratório de Helmintologia Romero Lascasas Porto, Departamento de Patologia e Laboratórios, Faculdade de Ciências Médicas, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Renata Heisler
authors.initials: RH
authors.lastname: Neves
authors.affiliation: Grupo de Genômica e Biologia Computacional, Instituto Nacional de Ciência e Tecnologia em Doenças Tropicais and Centro de Excelência em Bioinformática- CEBio, Centro de Pesquisas René Rachou, Fundação Oswaldo Cruz - FIOCRUZ, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Angela
authors.initials: A
authors.lastname: Volpini
authors.affiliation: Laboratório de Helmintologia Romero Lascasas Porto, Departamento de Patologia e Laboratórios, Faculdade de Ciências Médicas, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: José Roberto
authors.initials: JR
authors.lastname: Machado-Silva
authors.affiliation: Laboratório de Esquistossomose Centro de Pesquisas René Rachou, Fundação Oswaldo Cruz - FIOCRUZ, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Neusa
authors.initials: N
authors.lastname: Araujo
authors.affiliation: Laboratório de Entomologia Médica, Centro de Pesquisas René Rachou, Fundação Oswaldo Cruz - FIOCRUZ, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Rafael
authors.initials: R
authors.lastname: Nacif-Pimenta
authors.affiliation: Center for Discovery and Innovation in Parasitic Diseases, California Institute for Quantitative Biosciences and the Department of Pathology, University of California, San Francisco, San Francisco, California, United States of America.
authors.forename: Conor R
authors.initials: CR
authors.lastname: Caffrey
authors.affiliation: Grupo de Genômica e Biologia Computacional, Instituto Nacional de Ciência e Tecnologia em Doenças Tropicais and Centro de Excelência em Bioinformática- CEBio, Centro de Pesquisas René Rachou, Fundação Oswaldo Cruz - FIOCRUZ, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Guilherme
authors.initials: G
authors.lastname: Oliveira
mesh_terms: D000818:Animals; D005260:Female; D005298:Fertility; D005786:Gene Expression Regulation; D017238:Genes, Helminth; D015801:Helminth Proteins / Q000235:genetics / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D008297:Male; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D010053:Ovary / Q000254:growth & development; D010270:Parasite Egg Count; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D034622:RNA Interference; D012098:Reproduction; D012550:Schistosoma mansoni / Q000235:genetics / Q000254:growth & development*
chemical_list: D015801:Helminth Proteins; D047428:Protein Kinase Inhibitors; D020928:Mitogen-Activated Protein Kinases