ArticleScience signaling2013
AKT facilitates EGFR trafficking and degradation by phosphorylating and activating PIKfyve.
Article in Science signaling, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
59 citing papers in PubMed, 102 citations in OpenAlex.
- PTPN23 Overexpression Is Associated with Reduced Proliferation and Tumor Growth in Murine Models of Colorectal Cancer.International journal of molecular sciences · 2026Article
- Anti-EGFR therapy can overcome acquired resistance to the third-generation ALK-tyrosine kinase inhibitor lorlatinib mediated by activation of EGFR.Acta pharmacologica Sinica · 2025Article
- Phosphoinositide kinases in cancer: from molecular mechanisms to therapeutic opportunities.Nature reviews. Cancer · 2025Review
- The phospholipid kinase PIKFYVE is essential for Th17 differentiation.The Journal of experimental medicine · 2025Article
- Article
- Genome-wide CRISPR screens in spheroid culture reveal that the tumor suppressor LKB1 inhibits growth via the PIKFYVE lipid kinase.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Inhibition of EGFR Pathway Suppresses M1 Macrophage Polarization and Osteoclastogenesis, Mitigating Titanium Particle-Induced Bone Resorption.Journal of inflammation research · 2024Article
- Unveiling the impact of lysosomal ion channels: balancing ion signaling and disease pathogenesis.The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2023Review
- Domain-specific p53 mutants activate EGFR by distinct mechanisms exposing tissue-independent therapeutic vulnerabilities.Nature communications · 2023Article
- Endosomal trafficking inhibitor EGA can control TLR7-mediated IFNα expression by human plasmacytoid dendritic cells.Frontiers in immunology · 2023Article
- 25 Years of PI5P.Frontiers in cell and developmental biology · 2023Review
- Disruption of endosomal trafficking with EGA alters TLR9 cytokine response in human plasmacytoid dendritic cells.Frontiers in immunology · 2023Article
- ZLN005 improves the survival of polymicrobial sepsis by increasing the bacterial killingFrontiers in immunology · 2023Article
- Article
- Albumin Expands Albumin Reabsorption Capacity in Proximal Tubule Epithelial Cells through a Positive Feedback Loop between AKT and Megalin.International journal of molecular sciences · 2022Article
- Comprehensive Molecular Landscape of Cetuximab Resistance in Head and Neck Cancer Cell Lines.Cells · 2022Article
- Article
- Article
- Ebola virus triggers receptor tyrosine kinase-dependent signaling to promote the delivery of viral particles to entry-conducive intracellular compartments.PLoS pathogens · 2021Article
- MiRNAs in Gestational Diabetes Mellitus: Potential Mechanisms and Clinical Applications.Journal of diabetes research · 2021Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase (RTK) that controls cell proliferation, growth, survival, metabolism, and migration by activating the PI3K (phosphatidylinositol 3-kinase)-AKT and ERK (extracellular signal-regulated kinase)-RSK (ribosomal S6 kinase) pathways. EGFR signaling to these pathways is temporally and spatially regulated. Endocytic trafficking controls the access of EGFR to these downstream effectors and also its degradation, which terminates EGFR signaling. We showed that AKT facilitated the endocytic trafficking of EGFR to promote its degradation. Interfering with AKT signaling reduced both EGFR recycling and the rate of EGFR degradation. In AKT-impaired cells, EGFRs were unable to reach the cell surface or the lysosomal compartment and accumulated in the early endosomes, resulting in prolonged signaling and increased activation of ERK and RSK. Upon EGF stimulation, AKT phosphorylated and activated the kinase PIKfyve [FYVE-containing phosphatidylinositol 3-phosphate 5-kinase], which promoted vesicle trafficking to lysosomes. PIKfyve activation promoted EGFR degradation. Similar regulation occurred with platelet-derived growth factor receptor (PDGFR), suggesting that AKT phosphorylation and activation of PIKfyve is likely to be a common feedback mechanism for terminating RTK signaling and reducing receptor abundance.
Indexed as
Identifiers
What Socratic holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.