ArticleThe Journal of biological chemistry2011
Early endosomal antigen 1 (EEA1) is an obligate scaffold for angiotensin II-induced, PKC-alpha-dependent Akt activation in endosomes.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 54 citations in OpenAlex.
- Cholesterol-dependent control of endosomal escape regulates intracellular trafficking of small interfering RNA therapeutics and interactions with small molecule drugs.The Journal of pharmacology and experimental therapeutics · 2026Article
- Implications of Altered Endosomal-Lysosomal Biogenesis in Melanoma Pathogenesis.International journal of molecular sciences · 2025Review
- Domain-specific p53 mutants activate EGFR by distinct mechanisms exposing tissue-independent therapeutic vulnerabilities.Nature communications · 2023Article
- Computational modeling implicates protein scaffolding in p38 regulation of Akt.Journal of theoretical biology · 2022Article
- Glutamyl-prolyl-tRNA synthetase 1 coordinates early endosomal anti-inflammatory AKT signaling.Nature communications · 2022Article
- Microscopic image-based covariation network analysis for actin scaffold-modified insulin signaling.iScience · 2021Article
- Phosphorylation of Ykt6 SNARE Domain Regulates Its Membrane Recruitment and Activity.Biomolecules · 2020Article
- Article
- The role of mTOR pathway as target for treatment in adrenocortical cancer.Endocrine connections · 2019Review
- A large scale high-throughput screen identifies chemical inhibitors of phosphatidylinositol 4-kinase type II alpha.Journal of lipid research · 2019Article
- Getting the Akt Together: Guiding Intracellular Akt Activity by PI3K.Biomolecules · 2019Review
- Akt-ing Up Just About Everywhere: Compartment-Specific Akt Activation and Function in Receptor Tyrosine Kinase Signaling.Frontiers in cell and developmental biology · 2019Review
- Endocytosis is required for CThe Journal of biological chemistry · 2018Article
- The proximity-labeling technique BioID identifies sorting nexin 6 as a member of the insulin-like growth factor 1 (IGF1)-IGF1 receptor pathway.The Journal of biological chemistry · 2018Article
- Localization of mTORC2 activity inside cells.The Journal of cell biology · 2017Article
- Numb is involved in the non-random segregation of subcellular vesicles in colorectal cancer stem cells.Cell cycle (Georgetown, Tex.) · 2016Review
- mTORC1 Signaling Contributes to Drinking But Not Blood Pressure Responses to Brain Angiotensin II.Endocrinology · 2016Article
- Developmentally regulated GTP-binding protein 2 coordinates Rab5 activity and transferrin recycling.Molecular biology of the cell · 2016Article
- Subcellular trafficking of guanylyl cyclase/natriuretic peptide receptor-A with concurrent generation of intracellular cGMP.Bioscience reports · 2015Article
- The endosomal sorting complex required for transport pathway mediates chemokine receptor CXCR4-promoted lysosomal degradation of the mammalian target of rapamycin antagonist DEPTOR.The Journal of biological chemistry · 2015Article
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Akt/protein kinase B (PKB) activation/phosphorylation by angiotensin II (Ang II) is a critical signaling event in hypertrophy of vascular smooth muscle cells (VSMCs). Conventional wisdom asserts that Akt activation occurs mainly in plasma membrane domains. Recent evidence that Akt activation may take place within intracellular compartments challenges this dogma. The spatial identity and mechanistic features of these putative signaling domains have not been defined. Using cell fractionation and fluorescence methods, we demonstrate that the early endosomal antigen-1 (EEA1)-positive endosomes are a major site of Ang II-induced Akt activation. Akt moves to and is activated in EEA1 endosomes. The expression of EEA1 is required for phosphorylation of Akt at both Thr-308 and Ser-473 as well as for phosphorylation of its downstream targets mTOR and S6 kinase, but not for Erk1/2 activation. Both Akt and phosphorylated Akt (p-Akt) interact with EEA1. We also found that PKC-α is required for organizing Ang II-induced, EEA1-dependent Akt phosphorylation in VSMC early endosomes. EEA1 expression enables PKC-α phosphorylation, which in turn regulates Akt upstream signaling kinases, PDK1 and p38 MAPK. Our results indicate that PKC-α is a necessary regulator of EEA1-dependent Akt signaling in early endosomes. Finally, EEA1 down-regulation or expression of a dominant negative mutant of PKC-α blunts Ang II-induced leucine incorporation in VSMCs. Thus, EEA1 serves a novel function as an obligate scaffold for Ang II-induced Akt activation in early endosomes.
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Registered trials
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