ArticleScientific reports2018
GGA2 interacts with EGFR cytoplasmic domain to stabilize the receptor expression and promote cell growth.
Article in Scientific reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 26 citations in OpenAlex.
- Sorting of lysosomal enzyme and autophagy are regulated by the GGA1-induced TGN lipid scrambling.Science advances · 2026Article
- Establishment and validation of an ADP-ribosylation-related gene signature for prognostic prediction in lung adenocarcinoma.Discover oncology · 2026Article
- GGAs: Regulation of Multiple Sorting Pathways and Potential Association With Human Diseases.Journal of cellular and molecular medicine · 2026Review
- Exploring the Role of GGA2 in Cancer Progression: Pan-Cancer Bioinformatics and Experimental Validation in Prostate Cancer.International journal of molecular sciences · 2026Article
- Genome-Wide Genetic Analysis of Dropout in a Controlled Exercise Intervention in Sedentary Adults With Overweight or Obesity and Cardiometabolic Disease.Annals of behavioral medicine : a publication of the Society of Behavioral Medicine · 2024Article
- Endosomal protein expression of γ1-adaptin is associated with tumor growth activity and relapse-free survival in breast cancer.Breast cancer (Tokyo, Japan) · 2024Article
- Prostate cancer genetic risk and associated aggressive disease in men of African ancestry.Nature communications · 2023Article
- Protein sorting from endosomes to the TGN.Frontiers in cell and developmental biology · 2023Review
- Influence of EGF and pro-NGF on EGFR/SORTILIN interaction and clinical impact in head and neck squamous cell carcinoma.Frontiers in oncology · 2023Article
- Deciphering associations between three RNA splicing-related genetic variants and lung cancer risk.NPJ precision oncology · 2022Article
- Retrograde transport of CDMPR depends on several machineries as analyzed by sulfatable nanobodies.Life science alliance · 2022Article
- Cdc42 regulates cytokine expression and trafficking in bronchial epithelial cells.Frontiers in immunology · 2022Article
- Clathrin adapters AP-1 and GGA2 support expression of epidermal growth factor receptor for cell growth.Oncogenesis · 2021Article
- Inactivation of the three GGA genes in HeLa cells partially compromises lysosomal enzyme sorting.FEBS open bio · 2021Article
- Deficiency of GABARAP but not its Paralogs Causes Enhanced EGF-induced EGFR Degradation.Cells · 2020Article
- A Naturally Occurring Splice Variant of GGA1 Inhibits the Anterograde Post-Golgi Traffic of αScientific reports · 2019Article
- Cargo Sorting at theCells · 2019Review
- Integrative Genomic Analyses Identifies GGA2 as a Cooperative Driver of EGFR-Mediated Lung Tumorigenesis.Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer · 2019Article
Corrections and comments
- Erratum issued
Authors and funding
3 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Epidermal growth factor receptor (EGFR) signaling and its downregulation upon ligand binding have been extensively documented. However, the mechanisms by which cells maintain steady-state EGFR expression remain poorly understood. Here, we report a novel role of Golgi-localized, γ-adaptin ear-containing, ADP ribosylation factor-binding protein 2 (GGA2) in the control of EGFR turnover. Whereas GGA1- or GGA3-depletion increased EGFR expression, GGA2-depletion by RNAi greatly reduced steady-state expression of EGFR, reflecting enhanced lysosomal degradation of EGFR. Subsequent pull-down assays showed interactions of VHS-GAT domains from three GGAs with the cytoplasmic juxtamembrane region (jxt) of EGFR, which was dependent on N108 in the VHS domain. Proximity ligation assay also revealed the steady-state interaction between GGA2 and EGFR in situ. Moreover, reduced expression of EGFR in GGA2-depleted cells was reversed by additional depletion of GGA1 or GGA3, suggesting that GGA1 and GGA3 promote EGFR degradation. In addition, GGA2-depleted cells had reduced EGF signaling and cell proliferation in cell culture and xenograft experiments. Finally, GGA2 was upregulated in 30.8% of human hepatocellular carcinomas and 23.3% of colorectal cancers. Together, these results indicate that GGA2 supports cell growth by interacting with EGFR for sustaining the receptor expression.
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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 OpenQuestion graph.