ReviewCell cycle (Georgetown, Tex.)2017
The GAPs, GEFs, GDIs and…now, GEMs: New kids on the heterotrimeric G protein signaling block.
Review in Cell cycle (Georgetown, Tex.), 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 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
34 citing papers in PubMed, 49 citations in OpenAlex.
- Distinct colitis-associated macrophages drive NOD2-dependent bacterial sensing and gut homeostasis.The Journal of clinical investigation · 2025Article
- The Glyco-Switch of life: O-GlcNAcylation in cell fate decision.Glycobiology · 2025Review
- The RhoGDIβ-Rac1-CARD9 Signaling Module Mediates Islet β-Cell Dysfunction Under Chronic Hyperglycemia.Cells · 2025Review
- Tackling Undruggable Targets with Designer Peptidomimetics and Synthetic Biologics.Chemical reviews · 2024Review
- Trade-Off Regulation in Plant Growth and Stress Responses Through the Role of Heterotrimeric G Protein Signaling.Plants (Basel, Switzerland) · 2024Review
- Mycobacterium smegmatis MfpC is a GEF that regulates mfpA translationally to alter the fluoroquinolone efficacy.Communications biology · 2024Article
- Design, synthesis, and analysis of macrobicyclic peptides for targeting the Gαi protein.Journal of peptide science : an official publication of the European Peptide Society · 2024Article
- Heterotrimeric G protein signaling without GPCRs: The Gα-binding-and-activating (GBA) motif.The Journal of biological chemistry · 2024Review
- Bicyclic Peptide Library Screening for the Identification of Gαi Protein Modulators.Journal of medicinal chemistry · 2023Article
- Subcellular location defines GPCR signal transduction.Science advances · 2023Article
- Mycobacterium Fluoroquinolone Resistance Protein D (MfpD), a GTPase-Activating Protein of GTPase MfpB, Is Involved in Fluoroquinolones Potency.Microbiology spectrum · 2022Article
- Article
- Targeting Gαi/s Proteins with Peptidyl Nucleotide Exchange Modulators.ACS chemical biology · 2022Article
- Review
- Strategies towards Targeting Gαi/s Proteins: Scanning of Protein-Protein Interaction Sites To Overcome Inaccessibility.ChemMedChem · 2021Review
- Stability Analysis of a Signaling Circuit with Dual Species of GTPase Switches.Bulletin of mathematical biology · 2021Article
- Receptor tyrosine kinases activate heterotrimeric G proteins via phosphorylation within the interdomain cleft of Gαi.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- TLR4 signaling and macrophage inflammatory responses are dampened by GIV/Girdin.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Regulating cellular cyclic adenosine monophosphate: "Sources," "sinks," and now, "tunable valves".Wiley interdisciplinary reviews. Systems biology and medicine · 2020Review
- GIV/Girdin and Exo70 Collaboratively Regulate the Mammalian Polarized Exocytic Machinery.iScience · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
The canonical process of activation of heterotrimeric G proteins by G protein coupled receptors (GPCRs) is well studied. Recently, a rapidly emerging paradigm has revealed the existence of a new, non-canonical set of cytosolic G protein modulators, guanine exchange modulators (GEMs). Among G proteins regulators, GEMs are uniquely capable of initiating pleiotropic signals: these bifunctional modulators can activate cAMP inhibitory (Gi) proteins and inhibit cAMP-stimulatory (Gs) proteins through a single short evolutionarily conserved module. A prototypical member of the GEM family, GIV/Girdin, integrates signals downstream of a myriad of cell surface receptors, e.g., growth factor RTKs, integrins, cytokine, GPCRs, etc., and translates these signals into G protein activation or inhibition. By their pleiotropic action, GIV and other GEMs modulate several key pathways within downstream signaling network. Unlike canonical G protein signaling that is finite and is triggered directly and exclusively by GPCRs, the temporal and spatial features of non-canonical activation of G protein via GIV-family of cytosolic GEMs are unusually relaxed. GIV uses this relaxed circuitry to integrate, reinforce and compartmentalize signals downstream of both growth factors and G proteins in a way that enables it to orchestrate cellular phenotypes in a sustained manner. Mounting evidence suggests the importance of GIV and other GEMs as disease modulators and their potential to serve as therapeutic targets; however, a lot remains unknown within the layers of the proverbial onion that must be systematically peeled. This perspective summarizes the key concepts of the GEM-dependent G protein signaling paradigm and discusses the multidisciplinary approaches that are likely to revolutionize our understanding of this paradigm from the atomic level to systems biology.
Indexed as
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What OpenQuestion 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 OpenQuestion graph.