Please use this identifier to cite or link to this item:
https://hdl.handle.net/2440/130639
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Type: | Journal article |
Title: | Phosphorylation of PKCδ by FER tips the balance from EGFR degradation to recycling |
Other Titles: | Phosphorylation of PKCdelta by FER tips the balance from EGFR degradation to recycling |
Author: | Lonic, A. Gehling, F. Belle, L. Li, X. Schieber, N.L. Nguyen, E.V. Goodall, G.J. Parton, R.G. Daly, R.J. Khew-Goodall, Y. |
Citation: | Journal of Cellular Biochemistry, 2021; 220(2):1-27 |
Publisher: | Wiley |
Issue Date: | 2021 |
ISSN: | 0730-2312 1540-8140 |
Statement of Responsibility: | Ana Lonic, Freya Gehling, Leila Belle, Xiaochun Li, Nicole L. Schieber, Elizabeth V. Nguyen ... et al. |
Abstract: | Receptor degradation terminates signaling by activated receptor tyrosine kinases. Degradation of EGFR occurs in lysosomes and requires the switching of RAB5 for RAB7 on late endosomes to enable their fusion with the lysosome, but what controls this critical switching is poorly understood. We show that the tyrosine kinase FER alters PKCδ function by phosphorylating it on Y374, and that phospho-Y374-PKCδ prevents RAB5 release from nascent late endosomes, thereby inhibiting EGFR degradation and promoting the recycling of endosomal EGFR to the cell surface. The rapid association of phospho-Y374-PKCδ with EGFR-containing endosomes is diminished by PTPN14, which dephosphorylates phospho-Y374-PKCδ. In triple-negative breast cancer cells, the FER-dependent phosphorylation of PKCδ enhances EGFR signaling and promotes anchorage-independent cell growth. Importantly, increased Y374-PKCδ phosphorylation correlating with arrested late endosome maturation was identified in ∼25% of triple-negative breast cancer patients, suggesting that dysregulation of this pathway may contribute to their pathology. |
Keywords: | Cell Line, Tumor Endosomes Humans Breast Neoplasms Epidermal Growth Factor rab GTP-Binding Proteins Extracellular Signal-Regulated MAP Kinases Phosphotyrosine RNA, Messenger Mitogens Endocytosis Enzyme Activation Protein Transport Phosphorylation Time Factors Female Protein Kinase C-delta Protein-Tyrosine Kinases Protein Tyrosine Phosphatases, Non-Receptor Ubiquitination Protein Stability Proteolysis ErbB Receptors |
Rights: | © 2021 Lonic et al. This article is available under a Creative Commons License (Attribution 4.0 International, as described at https://creativecommons.org/licenses/by/4.0/). |
DOI: | 10.1083/jcb.201902073 |
Grant ID: | http://purl.org/au-research/grants/nhmrc/1146087 http://purl.org/au-research/grants/nhmrc/1089567 http://purl.org/au-research/grants/nhmrc/1037320 http://purl.org/au-research/grants/nhmrc/1058565 http://purl.org/au-research/grants/nhmrc/569542 http://purl.org/au-research/grants/nhmrc/1058540 http://purl.org/au-research/grants/nhmrc/1118170 |
Published version: | http://dx.doi.org/10.1083/jcb.201902073 |
Appears in Collections: | Aurora harvest 8 Medicine publications |
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hdl_130639.pdf | 8.48 MB | Adobe PDF | View/Open |
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