A new mechanism of EGFR activation identified by Phos-tag band shift analysis
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- Tanaka Tomohiro
- Department of Cancer Cell Biology, Faculty of Pharmaceutical Sciences, University of Toyama
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- Zhou Yue
- Department of Cancer Cell Biology, Faculty of Pharmaceutical Sciences, University of Toyama
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- Sakurai Hiroaki
- Department of Cancer Cell Biology, Faculty of Pharmaceutical Sciences, University of Toyama
Bibliographic Information
- Other Title
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- Phos-tag解析から見えてきた新しいEGFR活性化機構
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Abstract
<p>It has yet to be established whether ligand-unoccupied receptors remain on the plasma membrane or have any functions following a stimulation with ligand. We demonstrated that the minimal activation of EGFR tyrosine kinase by low concentration of EGF is sufficient to fully activate downstream MAPK pathways. Phos-tag band shift assay revealed that most of the remaining EGFR molecules were efficiently phosphorylated at serine/threonine residues by activated p38. The non-canonical p38 phosphorylation of the C-tail around Ser-1015 induced the clathrin-mediated endocytosis of unliganded EGFR monomers, which occurred slightly later than the canonical endocytosis of ligand-bound EGFR dimers via tyrosine autophosphorylation. Endocytosed EGFR via the non-canonical pathway was largely recycled back to the plasma membrane as functional receptors, whereas p38-independent populations were mainly sorted for lysosomal degradation. These results demonstrated that ligand-activated EGFR signaling controls unliganded receptors by feedback phosphorylation, identifying the dual-mode regulation of the endocytic trafficking dynamics of EGFR.</p>
Journal
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- Electrophoresis Letters
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Electrophoresis Letters 64 (1), 45-48, 2020
Japanese Electrophoresis Society
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Keywords
Details 詳細情報について
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- CRID
- 1390003825196961664
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- NII Article ID
- 130007871301
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- ISSN
- 21892636
- 21892628
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- Text Lang
- ja
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- Data Source
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- JaLC
- Crossref
- CiNii Articles
- KAKEN
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- Abstract License Flag
- Disallowed