ReviewFrontiers in cell and developmental biology2019
Ubiquitination as a Key Regulator of Endosomal Signaling by GPCRs.
Review in Frontiers in cell and developmental biology, 2019. 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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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
16 citing papers in PubMed, 25 citations in OpenAlex.
- E3 ligase RNF145 regulates airway smooth muscle cell proliferation via the PP2A-p70S6K signaling axis.The Journal of biological chemistry · 2026Article
- NEDD4L knockdown enhances synovial fibroblast migration, invasion, and inflammatory factor secretion via Wnt/β-Catenin signaling activation.Clinical rheumatology · 2026Article
- Unanchored K63-linked polyubiquitin chains: a novel second messenger involved in G protein-coupled receptors early signaling events.Cell communication and signaling : CCS · 2026Article
- Leveraging Targeted Protein Degradation for G Protein-Coupled Receptors: The Development of CCR2 Molecular Degraders.Journal of medicinal chemistry · 2025Article
- Endosomal catabolism of phosphatidylinositol 4,5-bisphosphate is fundamental in building resilience against pathogens.Protein & cell · 2025Article
- Editorial: Regulation of hormone and growth factor signalling by ubiquitin and ubiquitin-like protein modifications.Frontiers in endocrinology · 2024Article
- Fluorescence resonance energy transfer (FRET) spatiotemporal mapping of atypical P38 reveals an endosomal and cytosolic spatial bias.Scientific reports · 2023Article
- cFLIPCardiovascular drugs and therapy · 2023Article
- SP600125 Enhances Temperature-Controlled Repeated Thermal Stimulation-Induced Neurite Outgrowth in PC12-P1F1 Cells.International journal of molecular sciences · 2022Article
- Adenosine AMolecular biology reports · 2022Review
- Aldosterone breakthrough from a pharmacological perspective.Hypertension research : official journal of the Japanese Society of Hypertension · 2022Review
- ADAM10 Site-Dependent Biology: Keeping Control of a Pervasive Protease.International journal of molecular sciences · 2021Review
- Atypical p38 Signaling, Activation, and Implications for Disease.International journal of molecular sciences · 2021Review
- USP7 promotes hepatoblastoma progression through activation of PI3K/AKT signaling pathway.Cancer biomarkers : section A of Disease markers · 2021Article
- ASF1B promotes cervical cancer progression through stabilization of CDK9.Cell death & disease · 2020Article
- Beyond the Cell Surface: Targeting Intracellular Negative Regulators to Enhance T cell Anti-Tumor Activity.International journal of molecular sciences · 2019Review
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
G protein-coupled receptors (GPCRs) represent the largest family of therapeutic targets for FDA approved drugs. Therefore, understanding the molecular regulation of their signaling pathways is of paramount importance. Similarly, the mitogen activated protein kinase (MAPK) p38 is a critical mediator of proinflammatory disease. Yet despite decades of intense investigation, therapeutically viable inhibitors have struggled to make it into the clinic. New studies describing the regulation and activation of a GPCR dependent atypical p38 signaling pathway represents a novel therapeutic avenue to the treatment of many proinflammatory disorders. These recent studies have defined how thrombin and ADP can induce Src dependent activation of the E3 ubiquitin ligase NEDD4-2. Src dependent phosphorylation of a 2,3-linker peptide releases NEDD4-2 auto-inhibition and triggers the induction of proinflammatory atypical p38 signaling from the endosome. Activation of the atypical p38 pathway requires the direct interaction between an adaptor protein TAB1 and p38, that bypasses the requirement for the classical MKK3/6 dependent activation of p38. Therefore, providing a mechanism to specifically block proinflammatory GPCR atypical p38 activation while leaving basic p38 activity intact. Critically, new studies demonstrated that disruption of the TAB1-p38 interface is a druggable target, that would enable the selective inhibition of proinflammatory p38 signaling and ischemic injury. Atypical p38 signaling is linked to multiple clinically relevant pathologies including inflammation, cardiotoxicity, myocardial ischemia and ischemia reperfusion injury. Therefore, GPCR induced endosomal p38 signaling represents a novel understudied branch of proinflammatory p38 signaling and an ideal potential therapeutic target that warrants further investigation.
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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 Socratic graph.