GEFs and GAPs: Critical Elements in the Control of Small G Proteins
Open accessAbstract
Guanine nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs) regulate the activity of small guanine nucleotide-binding (G) proteins to control cellular functions. In general, GEFs turn on signaling by catalyzing the exchange from G-protein-bound GDP to GTP, whereas GAPs terminate signaling by inducing GTP hydrolysis. GEFs and GAPs are multidomain proteins that are regulated by extracellular signals and localized cues that control cellular events in time and space. Recent evidence suggests that these proteins may be potential therapeutic targets for developing drugs to treat various diseases, including cancer.
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RalA and RalB are activated by GEFs and inactivated by GAPs that consist of a regulatory β-subunit (RalGAPB) and one of two catalytic α-subunits, RalGAPA1 or RalGAPA2.
“RalA and RalB are activated by guanine nucleotide exchange factors (GEFs) and inactivated by GTPase-activating proteins (GAPs) that consist of a regulatory β-subunit (RalGAPB) and one of two catalytic α-subunits, RalGAPA1 or RalGAPA2 (refs. 15,16).”
From Dietary cholesterol activates a Ral-dependent pathway driving LDLR turnover (2026) · cites this paper as [16]
Due to high amino acid sequence similarity among Rho GTPases, many identified GEFs and GAPs show only limited binding specificity, making spatiotemporal regulation necessary to allow specific signaling.
“Due to the high amino acid sequence similarity among the Rho GTPases, however, many of the identified GEFs and GAPs show only limited binding specificity, which makes spatiotemporal regulation necessary to allow specific signaling [17].”
From RhoA Signaling in Neurodegenerative Diseases (2022) · cites this paper as [17]
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- Authors
- Bos, J. L., Rehmann, H., & Wittinghofer, A.
- Affiliations
- University Medical Center Utrecht (NL)
- Max Planck Institute of Molecular Physiology (DE)
- Corresponding author
- Bos, Johannes L.
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2007-06
- Volume
- 129
- Issue
- 5
- Pages
- 865-877
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W1993735775
- Cited by
- 1,903
- References
- 1
- Citations by year
- 2026: 86 · 2025: 116 · 2024: 108 · 2023: 116 · 2022: 115 · 2021: 119 · 2020: 106 · 2019: 104 · 2018: 101 · 2017: 104 · 2016: 118 · 2015: 85 · 2014: 91 · 2013: 108 · 2012: 90
- FWCI
- 6.48
- Type
- journal article
- Language
- en
- Update notices
- erratum (2007-07-27)
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Max Planck Institute for Plasma Physics (submittedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
- Keywords
- guanine nucleotide exchange factor, GTPase-activating protein, small GTPases, G protein signaling, GTP hydrolysis, signal termination, therapeutic target, cancer
- MeSH terms
- Animals, Humans, Models, Molecular, Neoplasms, Signal Transduction, Monomeric GTP-Binding Proteins, Guanine Nucleotide Exchange Factors, GTPase-Activating Proteins
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