| Author | Andrade, Warrison Athanásio Coelho de | |
| Author | Silva, Aristóbolo Mendes da | |
| Author | Alves, Viviane S. | |
| Author | Salgado, Ana Paula Carneiro | |
| Author | Melo, M. B. | |
| Author | Andrade, Hélida Monteiro de | |
| Author | Dall’Orto, F. V. | |
| Author | Garcia, S. A. | |
| Author | Silveira, Tatiana Nunes | |
| Author | Gazzinelli, Ricardo Tostes | |
| Access date | 2013-08-28T16:28:04Z | |
| Available date | 2013-08-28T16:28:04Z | |
| Document date | 2010 | |
| Citation | ANDRADE, Warrison Athanásio Coelho de et al. Early endosome localization and activity of RasGEF1b, a toll-like receptor-inducible Ras guanine-nucleotide exchange factor. Genes Immun., v. 11, n. 6, p. 447-457, 2010. | pt_BR |
| ISSN | 1466-4879 | |
| URI | https://www.arca.fiocruz.br/handle/icict/6834 | |
| Language | eng | pt_BR |
| Publisher | Nature | pt_BR |
| Rights | restricted access | |
| Title | Early endosome localization and activity of RasGEF1b, a toll-like receptor-inducible Ras guanine-nucleotide exchange factor | pt_BR |
| Type | Article | |
| Abstract | Guanine-nucleotide exchange factors (GEFs) stimulate the intrinsic GDP/GTP exchange activity of Ras and promote the formation of active Ras–GTP, which in turn controls diverse signalling networks important for the regulation of cell proliferation, survival, differentiation, vesicular trafficking, and gene expression. RasGEF1b is a GEF, whose expression is induced in macrophages on stimulation with toll-like receptor (TLR) agonists. Here, we showed that in vitro RasGEF1b expression by macrophages is mostly induced by TLR3 (poly I:C) and TLR4 (lipopolysaccharyde) through the MyD88-independent pathway.
In vivo infection with the protozoan parasites Trypanosoma cruzi and Plasmodium chabaudi induced RasGEF1b in an MyD88-, TRIF-, and IFN-g-dependent manner. Ectopically expressed RasGEF1b was found, mostly, in the heavy membrane fraction of HEK 293T, and by confocal microscopy, it was found to be located at early endosomes. Computational modelling of the RasGEF1b–Ras interaction revealed that RasGEF1b interacts with the binding domain site of Ras, a critical region for interacting with GEFs involved in the activation of Ras-Raf-MEK-ERK pathway. More important, RasGEF1b was found to be closely associated with Ras in live cells and to trigger Ras activity. Altogether, these results indicate that on TLR activation, RasGEF1b may trigger Ras-like proteins and regulate specific biological activities described for this subtype of GTPases | pt_BR |
| Affilliation | Federal University of Minas Gerais. Department of Biochemistry and Immunology. MG, Brazil. | pt_BR |
| Affilliation | Federal University of Minas Gerais. Department of Morphology. MG, Brazil/Oswaldo Cruz Foundation. Rene Rachou Research Center. Belo Horizonte, MG, Brazil. | pt_BR |
| Affilliation | Oswaldo Cruz Foundation. Rene Rachou Research Center. Belo Horizonte, MG, Brazil. | pt_BR |
| Affilliation | Federal University of Minas Gerais. Department of Biochemistry and Immunology. MG, Brazil. | pt_BR |
| Affilliation | University of Massachusetts. Medical School. Worcester, MA, USA | pt_BR |
| Affilliation | Federal University of Minas Gerais. Department of Biochemistry and Immunology. MG, Brazil. | pt_BR |
| Affilliation | Federal University of Minas Gerais. Department of Morphology. Minas Gerais, Brazil. | pt_BR |
| Affilliation | Oswaldo Cruz Foundation. Rene Rachou Research Center. Belo Horizonte, MG, Brazil. | pt_BR |
| Affilliation | Oswaldo Cruz Foundation. Rene Rachou Research Center. Belo Horizonte, MG, Brazil. | pt_BR |
| Affilliation | Federal University of Minas Gerais. Department of Biochemistry and Immunology. MG, Brazil/ Oswaldo Cruz Foundation. Rene Rachou Research Center. Belo Horizonte, MG, Brazil/University of Massachusetts. Medical School. Worcester, MA, USA. | pt_BR |
| Subject | cell signalling | pt_BR |
| Subject | TLR | pt_BR |
| Subject | expression | pt_BR |
| Subject | RasGEF1b | pt_BR |
| Subject | Ras | pt_BR |
