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Re-localization of activated EGF receptor and its signal transducers to multivesicular compartments downstream of early endosomes in response to EGF.
Oksvold, M P; Skarpen, E; Wierød, L; Paulsen, R E; Huitfeldt, H S.
Afiliación
  • Oksvold MP; Institute of Pathology, The National Hospital, University of Oslo, Norway. m.p.oksvold@labmed.uio.no
Eur J Cell Biol ; 80(4): 285-94, 2001 Apr.
Article en En | MEDLINE | ID: mdl-11370743
The rapid internalization of receptor tyrosine kinases after ligand binding has been assumed to be a negative modulation of signal transduction. However, accumulating data indicate that signal transduction from internalized cell surface receptors also occurs from endosomes. We show that a substantial fraction of tyrosine-phosphorylated epidermal growth factor receptor (EGFR) and Shc, Grb2 and Cbl after internalization relocates from early endosomes to compartments which are negative for the early endosomes, recycling vesicle markers EEA1 and transferrin in EGF-stimulated cells. These compartments contained the multivesicular body and late endosome marker CD63, and the late endosome and lysosome marker LAMP-1, and showed a multivesicular morphology. Subcellular fractionation revealed that activated EGFR, adaptor proteins and activated ERK 1 and 2 were located in EEA1-negative and LAMP-1-positive fractions. Co-immunoprecipitations showed EGFR in complex with both Shc, Grb2 and Cbl. Treatment with the weak base chloroquine or inhibitors of lysosomal enzymes after EGF stimulation induced an accumulation of tyrosine-phosphorylated EGFR and Shc in EEA1-negative and CD63-positive vesicles after a 120-min chase period. This was accompanied by a sustained activation of ERK 1 and 2. These results suggest that EGFR signaling is not spatially restricted to the plasma membrane, primary vesicles and early endosomes, but is continuing from late endocytic trafficking organelles maturing from early endosomes.
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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Endosomas / Transducción de Señal / Ubiquitina-Proteína Ligasas / Proteínas Adaptadoras Transductoras de Señales / Factor de Crecimiento Epidérmico / Receptores ErbB Idioma: En Revista: Eur J Cell Biol Año: 2001 Tipo del documento: Article País de afiliación: Noruega Pais de publicación: Alemania
Buscar en Google
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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Endosomas / Transducción de Señal / Ubiquitina-Proteína Ligasas / Proteínas Adaptadoras Transductoras de Señales / Factor de Crecimiento Epidérmico / Receptores ErbB Idioma: En Revista: Eur J Cell Biol Año: 2001 Tipo del documento: Article País de afiliación: Noruega Pais de publicación: Alemania