Assuntos
Infecções por Adenovirus Humanos/diagnóstico , Infecções por Adenovirus Humanos/tratamento farmacológico , Adenovírus Humanos/isolamento & purificação , Infecções por Adenovirus Humanos/imunologia , Antivirais/uso terapêutico , Pré-Escolar , Diagnóstico Diferencial , Quimioterapia Combinada , Feminino , Febre/etiologia , Humanos , Imunocompetência/imunologia , Linfo-Histiocitose Hemofagocítica/diagnóstico , Linfo-Histiocitose Hemofagocítica/imunologia , Reação em Cadeia da Polimerase , Resultado do TratamentoAssuntos
Anemia/tratamento farmacológico , Eritropoetina , Proteínas Tirosina Quinases/metabolismo , Proteínas Proto-Oncogênicas , Receptores da Eritropoetina/metabolismo , Eritropoetina/metabolismo , Eritropoetina/fisiologia , Eritropoetina/uso terapêutico , Humanos , Janus Quinase 2 , Receptores da Eritropoetina/fisiologia , Transdução de SinaisRESUMO
Erythropoietin (EPO) promotes viability, proliferation and differentiation of mammalian erythroid progenitor cells via its specific cell surface receptor (EPO-R). We have previously shown that truncated EPO-Rs containing 267 amino acids or less were defective in internalization of (125)I-EPO, whereas internalization via a receptor derivative containing 276 amino acids was unaffected, thus directing focus to the nine amino acid residues FEGLFTTHK at positions 268-276 [Levin, Cohen, Supino, Yoshimura, Watowich, Neumann, FEBS Lett. 427 (1998) 164-170]. Here, a panel of EPO-R mutants was generated to determine the role of these residues in EPO endocytosis, down regulation of cell surface receptors and EPO-mediated signaling. While linking amino acid residues 268-276 to a truncated EPO-R (Delta+9 EPO-R) conferred both ligand uptake and ligand-independent down regulation of the respective receptor from the cell surface, Phe 272 was crucial for EPO endocytosis but not for ligand-independent down regulation. Additional receptor motifs probably play a role in EPO endocytosis and receptor down-regulation, as these processes were not adversely impaired in Delta268-276 EPO-R. A central role of residues 268-276, in particular Phe, was demonstrated by the inability of Delta268-276 and F268,272A EPO-Rs to support EPO-mediated signal transduction.