title: Identification and characterization of a novel mouse gene encoding a Ras-associated guanine nucleotide exchange factor: expression in macrophages and myocarditis elicited by Trypanosoma cruzi parasites.
abstract: The ability of Trypanosoma cruzi to activate macrophages is, at least in part, attributed to the glycosylphosphatidylinositol-anchored mucin-like glycoproteins (GPI-mucins) expressed in the surface of the trypomastigote stage of the parasite. The differential display reverse transcriptase-polymerase chain reaction and the reverse Northern blot were used to study modulation of gene expression in murine macrophages exposed to GPI-mucins and in cardiac tissues from mice infected with T. cruzi. Among several cDNAs that were more abundant in lanes corresponding to macrophages stimulated with GPI-mucins as compared with resting cells, we confirmed the differential expression of A1, interleukin-18, and GPIgamma4. Some of these genes were also shown to have enhanced expression in the cardiac tissue (DAP-12, A1, and GPIgamma4) from infected animals. The expression of GPIgamma4 was also enhanced in human monocytes stimulated with GPI-mucins or bacterial lipopolysaccharides. The complete sequence of the GPIgamma4 transcript and its gene including the 5' upstream region was defined. GPIgamma4 was encoded by a novel, single copy gene present in mouse as well as human genomes and showed conserved homology to different members of the guanine nucleotide exchange factor family.
authors.affiliation: Department of Biochemistry and Immunology, Institute of Biological Sciences, Federal University of Minas Gerais, Brazil.
authors.forename: Ludmila R P
authors.initials: LR
authors.lastname: Ferreira
authors.forename: Eduardo F
authors.initials: EF
authors.lastname: Abrantes
authors.forename: Cibele V
authors.initials: CV
authors.lastname: Rodrigues
authors.forename: Braulia
authors.initials: B
authors.lastname: Caetano
authors.forename: Gustavo C
authors.initials: GC
authors.lastname: Cerqueira
authors.forename: Anna Christina
authors.initials: AC
authors.lastname: Salim
authors.forename: Luiz F L
authors.initials: LF
authors.lastname: Reis
authors.forename: Ricardo T
authors.initials: RT
authors.lastname: Gazzinelli
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D004268:DNA-Binding Proteins / Q000235:genetics; D040461:Gene Components; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D017261:Glycosylphosphatidylinositols; D006801:Humans; D020382:Interleukin-18 / Q000235:genetics; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins; D051379:Mice / Q000235:genetics*; D008969:Molecular Sequence Data; D009077:Mucins / Q000494:pharmacology; D009205:Myocarditis / Q000378:metabolism / Q000469:parasitology*; D011971:Receptors, Immunologic / Q000235:genetics; D051818:Replication Protein C; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D014349:Trypanosoma cruzi; D020663:ras Guanine Nucleotide Exchange Factors / Q000096:biosynthesis / Q000235:genetics*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D004268:DNA-Binding Proteins; D017261:Glycosylphosphatidylinositols; D020382:Interleukin-18; D008565:Membrane Proteins; D009077:Mucins; D011971:Receptors, Immunologic; C110546:TYROBP protein, human; D020663:ras Guanine Nucleotide Exchange Factors; D051818:Replication Protein C