title: Molecular analysis of Aedes aegypti classical protein tyrosine phosphatases uncovers an ortholog of mammalian PTP-1B implicated in the control of egg production in mosquitoes.
abstract: BACKGROUND
  Protein Tyrosine Phosphatases (PTPs) are enzymes that catalyze phosphotyrosine dephosphorylation and modulate cell differentiation, growth and metabolism. In mammals, PTPs play a key role in the modulation of canonical pathways involved in metabolism and immunity. PTP1B is the prototype member of classical PTPs and a major target for treating human diseases, such as cancer, obesity and diabetes. These signaling enzymes are, hence, targets of a wide array of inhibitors. Anautogenous mosquitoes rely on blood meals to lay eggs and are vectors of the most prevalent human diseases. Identifying the mosquito ortholog of PTP1B and determining its involvement in egg production is, therefore, important in the search for a novel and crucial target for vector control.
  
  
  RESULTS
  We conducted an analysis to identify the ortholog of mammalian PTP1B in the Aedes aegypti genome. We identified eight genes coding for classical PTPs. In silico structural and functional analyses of proteins coded by such genes revealed that four of these code for catalytically active enzymes. Among the four genes coding for active PTPs, AAEL001919 exhibits the greatest degree of homology with the mammalian PTP1B. Next, we evaluated the role of this enzyme in egg formation. Blood feeding largely affects AAEL001919 expression, especially in the fat body and ovaries. These tissues are critically involved in the synthesis and storage of vitellogenin, the major yolk protein. Including the classical PTP inhibitor sodium orthovanadate or the PTP substrate DiFMUP in the blood meal decreased vitellogenin synthesis and egg production. Similarly, silencing AAEL001919 using RNA interference (RNAi) assays resulted in 30% suppression of egg production.
  
  
  CONCLUSIONS
  The data reported herein implicate, for the first time, a gene that codes for a classical PTP in mosquito egg formation. These findings raise the possibility that this class of enzymes may be used as novel targets to block egg formation in mosquitoes.
authors.affiliation: Laboratório de Sinalização Celular (LabSiCel), Instituto de Bioquímica Médica Leopoldo de Meis, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil; Instituto Nacional de Ciência e Tecnologia em Entomologia Molecular (INCT-EM), Rio de Janeiro, RJ, Brazil.
authors.forename: Debora Monteiro
authors.initials: DM
authors.lastname: Moretti
authors.affiliation: Department of Pharmacology, University of California San Diego, San Diego, California, United States of America.
authors.forename: Lalima Gagan
authors.initials: LG
authors.lastname: Ahuja
authors.affiliation: Laboratório de Sinalização Celular (LabSiCel), Instituto de Bioquímica Médica Leopoldo de Meis, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil; Instituto Nacional de Ciência e Tecnologia em Entomologia Molecular (INCT-EM), Rio de Janeiro, RJ, Brazil.
authors.forename: Rodrigo Dutra
authors.initials: RD
authors.lastname: Nunes
authors.affiliation: Laboratório de Sinalização Celular (LabSiCel), Instituto de Bioquímica Médica Leopoldo de Meis, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil; Instituto Nacional de Ciência e Tecnologia em Entomologia Molecular (INCT-EM), Rio de Janeiro, RJ, Brazil.
authors.forename: Cecília Oliveira
authors.initials: CO
authors.lastname: Cudischevitch
authors.affiliation: Laboratório de Sinalização Celular (LabSiCel), Instituto de Bioquímica Médica Leopoldo de Meis, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil; Instituto Nacional de Ciência e Tecnologia em Entomologia Molecular (INCT-EM), Rio de Janeiro, RJ, Brazil.
authors.forename: Carlos Renato Oliveira
authors.initials: CR
authors.lastname: Daumas-Filho
authors.affiliation: Laboratório de Sinalização Celular (LabSiCel), Instituto de Bioquímica Médica Leopoldo de Meis, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil; Instituto Nacional de Ciência e Tecnologia em Entomologia Molecular (INCT-EM), Rio de Janeiro, RJ, Brazil.
authors.forename: Priscilla
authors.initials: P
authors.lastname: Medeiros-Castro
authors.affiliation: Laboratório de Sinalização Celular (LabSiCel), Instituto de Bioquímica Médica Leopoldo de Meis, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil; Instituto Nacional de Ciência e Tecnologia em Entomologia Molecular (INCT-EM), Rio de Janeiro, RJ, Brazil.
authors.forename: Guilherme
authors.initials: G
authors.lastname: Ventura-Martins
authors.affiliation: Laboratório de Sinalização Celular (LabSiCel), Instituto de Bioquímica Médica Leopoldo de Meis, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil; Instituto Nacional de Ciência e Tecnologia em Entomologia Molecular (INCT-EM), Rio de Janeiro, RJ, Brazil.
authors.forename: Willy
authors.initials: W
authors.lastname: Jablonka
authors.affiliation: Laboratório de Sinalização Celular (LabSiCel), Instituto de Bioquímica Médica Leopoldo de Meis, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil; Instituto Nacional de Ciência e Tecnologia em Entomologia Molecular (INCT-EM), Rio de Janeiro, RJ, Brazil.
authors.forename: Felipe
authors.initials: F
authors.lastname: Gazos-Lopes
authors.affiliation: Laboratório de Sinalização Celular (LabSiCel), Instituto de Bioquímica Médica Leopoldo de Meis, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil; Instituto Nacional de Ciência e Tecnologia em Entomologia Molecular (INCT-EM), Rio de Janeiro, RJ, Brazil.
authors.forename: Raquel
authors.initials: R
authors.lastname: Senna
authors.affiliation: Laboratório de Sinalização Celular (LabSiCel), Instituto de Bioquímica Médica Leopoldo de Meis, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil; Instituto Nacional de Ciência e Tecnologia em Entomologia Molecular (INCT-EM), Rio de Janeiro, RJ, Brazil.
authors.forename: Marcos Henrique Ferreira
authors.initials: MH
authors.lastname: Sorgine
authors.affiliation: Departamento de Biologia Celular e Molecular e Bioagentes Patogênicos, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, Brazil.
authors.forename: Klaus
authors.initials: K
authors.lastname: Hartfelder
authors.affiliation: Departamento de Parasitologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, Brazil.
authors.forename: Margareth
authors.initials: M
authors.lastname: Capurro
authors.affiliation: Laboratório de Sinalização Celular (LabSiCel), Instituto de Bioquímica Médica Leopoldo de Meis, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil; Instituto Nacional de Ciência e Tecnologia em Entomologia Molecular (INCT-EM), Rio de Janeiro, RJ, Brazil.
authors.forename: Georgia Correa
authors.initials: GC
authors.lastname: Atella
authors.affiliation: Departamento de Bioquímica, Instituto de Química, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil; Instituto Nacional de Ciência e Tecnologia em Entomologia Molecular (INCT-EM), Rio de Janeiro, RJ, Brazil.
authors.forename: Rafael Dias
authors.initials: RD
authors.lastname: Mesquita
authors.affiliation: Laboratório de Sinalização Celular (LabSiCel), Instituto de Bioquímica Médica Leopoldo de Meis, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil; Instituto Nacional de Ciência e Tecnologia em Entomologia Molecular (INCT-EM), Rio de Janeiro, RJ, Brazil.
authors.forename: Mário Alberto Cardoso
authors.initials: MA
authors.lastname: Silva-Neto
mesh_terms: D000330:Aedes / Q000187:drug effects / Q000201:enzymology* / Q000235:genetics; D000595:Amino Acid Sequence; D000818:Animals; D005216:Fat Body / Q000187:drug effects / Q000201:enzymology; D005260:Female; D005786:Gene Expression Regulation; D049750:Genome, Insect; D006923:Hymecromone / Q000031:analogs & derivatives / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010053:Ovary / Q000187:drug effects / Q000201:enzymology; D010058:Oviposition / Q000187:drug effects / Q000235:genetics*; D017434:Protein Structure, Tertiary; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1 / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D014638:Vanadates / Q000494:pharmacology; D014819:Vitellogenins / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics*
chemical_list: C119285:6,8-difluoro-4-methylumbelliferyl phosphate; D034741:RNA, Small Interfering; D014819:Vitellogenins; D006923:Hymecromone; D014638:Vanadates; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1