ArticleThe Journal of biological chemistry2015
The endosomal sorting complex required for transport pathway mediates chemokine receptor CXCR4-promoted lysosomal degradation of the mammalian target of rapamycin antagonist DEPTOR.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
What it found
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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.
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Who cites it
14 citing papers in PubMed, 26 citations in OpenAlex.
- ITIH4 alleviates OVA-induced asthma by regulating lung-gut microbiota.Molecular medicine (Cambridge, Mass.) · 2025Article
- Proximity Labeling to Identify β-Arrestin1 Binding Partners Downstream of Ligand-Activated G Protein-Coupled Receptors.International journal of molecular sciences · 2023Article
- Digital Display Precision Predictor: the prototype of a global biomarker model to guide treatments with targeted therapy and predict progression-free survival.NPJ precision oncology · 2021Article
- Glucagon's Metabolic Action in Health and Disease.Comprehensive Physiology · 2021Article
- Depletion of Ric-8B leads to reduced mTORC2 activity.PLoS genetics · 2020Article
- Metabolic regulation through the endosomal system.Traffic (Copenhagen, Denmark) · 2019Review
- ESCRT Proteins Control the Dendritic Morphology of Developing and Mature Hippocampal Neurons.Molecular neurobiology · 2019Article
- Heterologous regulation of CXCR4 lysosomal trafficking.The Journal of biological chemistry · 2019Article
- Mechanisms of the anterograde trafficking of GPCRs: Regulation of AT1R transport by interacting proteins and motifs.Traffic (Copenhagen, Denmark) · 2019Review
- Endocytosis is required for CThe Journal of biological chemistry · 2018Article
- DEPTOR at the Nexus of Cancer, Metabolism, and Immunity.Physiological reviews · 2018Review
- Molecular Genetics of Frontotemporal Dementia Elucidated byInternational journal of molecular sciences · 2018Review
- β-Arrestin1 and Signal-transducing Adaptor Molecule 1 (STAM1) Cooperate to Promote Focal Adhesion Kinase Autophosphorylation and Chemotaxis via the Chemokine Receptor CXCR4.The Journal of biological chemistry · 2016Article
- Postendocytic Sorting of Adrenergic and Opioid Receptors: New Mechanisms and Functions.Progress in molecular biology and translational science · 2015Review
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
G protein-coupled receptor (GPCR) signaling mediates many cellular functions, including cell survival, proliferation, and cell motility. Many of these processes are mediated by GPCR-promoted activation of Akt signaling by mammalian target of rapamycin complex 2 (mTORC2) and the phosphatidylinositol 3-kinase (PI3K)/phosphoinositide-dependent kinase 1 (PDK1) pathway. However, the molecular mechanisms by which GPCRs govern Akt activation by these kinases remain poorly understood. Here, we show that the endosomal sorting complex required for transport (ESCRT) pathway mediates Akt signaling promoted by the chemokine receptor CXCR4. Pharmacological inhibition of heterotrimeric G protein Gαi or PI3K signaling and siRNA targeting ESCRTs blocks CXCR4-promoted degradation of DEPTOR, an endogenous antagonist of mTORC2 activity. Depletion of ESCRTs by siRNA leads to increased levels of DEPTOR and attenuated CXCR4-promoted Akt activation and signaling, consistent with decreased mTORC2 activity. In addition, ESCRTs likely have a broad role in Akt signaling because ESCRT depletion also attenuates receptor tyrosine kinase-promoted Akt activation and signaling. Our data reveal a novel role for the ESCRT pathway in promoting intracellular signaling, which may begin to identify the signal transduction pathways that are important in the physiological roles of ESCRTs and Akt.
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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 OpenQuestion graph.