Journal
JOURNAL OF CELL SCIENCE
Volume 130, Issue 15, Pages 2481-2490Publisher
COMPANY OF BIOLOGISTS LTD
DOI: 10.1242/jcs.202358
Keywords
EGF receptor; p38 MAPK; Endocytosis; Nuclear translocation
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Funding
- Medical Research Council (MRC) [G1001684]
- Cancer Research UK [C2259/A16569]
- MRC [G1001684] Funding Source: UKRI
- Cancer Research UK [16569] Funding Source: researchfish
- Medical Research Council [G1001684] Funding Source: researchfish
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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.
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