Stress-specific p38 MAPK activation is sufficient to drive EGFR endocytosis but not its nuclear translocation.
J Cell Sci
; 130(15): 2481-2490, 2017 Aug 01.
Article
em En
| MEDLINE
| ID: mdl-28646091
ABSTRACT
EGF receptor (EGFR) endocytosis is induced by stress in a manner dependent on the p38 MAPK family. Ligand and stresses such as X-rays, reportedly promote nuclear trafficking of endocytosed EGFR for regulation of gene transcription and DNA repair. We fail to detect EGFR endocytosis or nuclear transport following X-ray treatment of HeLa or head and neck cancer cells, despite extensive DNA damage induction. Apparent nuclear staining with EGFR extracellular domain antibody remained present despite reduced/absent EGFR expression, and so did not represent nuclear EGFR. UVB and UVC, but not X-ray or UVA, treatment induced p38 activation and EGFR endocytosis, although all of these stresses induced DNA damage, indicating that DNA damage alone is not sufficient to induce EGFR endocytosis. Increased reactive oxygen species (ROS) levels following UVB treatment, compared to that seen with X-rays, do not alone explain differences in p38 activation. UVB, like UVC, induced EGFR accumulation predominantly in perinuclear endosomes, rather than in the nucleus. Our morphological techniques identifying major changes in receptor distribution do not exclude the possibility that small but biologically relevant amounts of EGFR enter the nucleus. This study highlights the importance and limitations of morphological analyses of receptor distribution in understanding signaling outcome.
Palavras-chave
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Raios Ultravioleta
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Raios X
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Núcleo Celular
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Proteínas Quinases p38 Ativadas por Mitógeno
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Endocitose
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Receptores ErbB
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Humans
Idioma:
En
Revista:
J Cell Sci
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
Reino Unido