ArticleThe Journal of cell biology2021
Phosphorylation of PKCδ by FER tips the balance from EGFR degradation to recycling.
Article in The Journal of cell biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 25 citations in OpenAlex.
- Oncogenic receptor tyrosine kinase signaling is driven by the Golgi protein GOLPH3 and its interaction with MYO18A.Science signaling · 2026Article
- LncRNA EUDAL shapes tumor cell response to hypoxia-induced constitutive EGFR activation and promotes chemoresistance in oral cancer.International journal of oral science · 2025Article
- EGF receptor in organ development, tissue homeostasis and regeneration.Journal of biomedical science · 2025Review
- VASH2 enhances KIF3C-mediated EGFR-endosomal recycling to promote aggression and chemoresistance of lung squamous cell carcinoma by increasing tubulin detyrosination.Cell death & disease · 2024Article
- PTPN14 aggravates neointimal hyperplasia via boosting PDGFRβ signaling in smooth muscle cells.Nature communications · 2024Article
- mRNA-Lipid Nanoparticle-Mediated Restoration of PTPN14 Exhibits Antitumor Effects by Overcoming Anoikis Resistance in Triple-Negative Breast Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Article
- The receptor protein tyrosine phosphatase PTPRK promotes intestinal repair and catalysis-independent tumour suppression.Journal of cell science · 2024Article
- Optimization of Novel Pyrido-pyridazinone Derivatives as FER Tyrosine Kinase Inhibitors, Leading to the Potent DS08701581.ACS medicinal chemistry letters · 2024Article
- EGFR endocytosis: more than meets the eye.Oncotarget · 2023Article
- The pseudokinase NRBP1 activates Rac1/Cdc42 via P-Rex1 to drive oncogenic signalling in triple-negative breast cancer.Oncogene · 2023Article
- Network models of protein phosphorylation, acetylation, and ubiquitination connect metabolic and cell signaling pathways in lung cancer.PLoS computational biology · 2023Article
- Deciphering the Role and Signaling Pathways of PKCα in Luminal A Breast Cancer Cells.International journal of molecular sciences · 2022Article
- Quantifying EGFR endosomal recycling via immunofluorescence in breast cancer cells.STAR protocols · 2022Article
- Inhibitory role of proguanil on the growth of bladder cancer via enhancing EGFR degradation and inhibiting its downstream signaling pathway to induce autophagy.Cell death & disease · 2022Article
- Multiple roles for actin in secretory and endocytic pathways.Current biology : CB · 2021Review
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
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.
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Registered trials
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