ArticleThe Journal of biological chemistry2012
The pleckstrin homology (PH) domain of the Arf exchange factor Brag2 is an allosteric binding site.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 40 citations in OpenAlex.
- ARHGEF7 S-glutathionylation promotes cancer cell migration through Rac1 activation.bioRxiv : the preprint server for biology · 2026Article
- Characterization of the small Arabidopsis thaliana GTPase and ADP-ribosylation factor-like 2 protein TITAN 5.Journal of cell science · 2024Article
- Characterization of the smallbioRxiv : the preprint server for biology · 2024Article
- The Abl-interactor Abi suppresses the function of the BRAG2 GEF family member Schizo.Biology open · 2024Article
- Article
- Ca2+-induced release of IQSEC2/BRAG1 autoinhibition under physiological and pathological conditions.The Journal of cell biology · 2023Article
- Arf6 as a therapeutic target: Structure, mechanism, and inhibitors.Acta pharmaceutica Sinica. B · 2023Review
- Characterization and computational simulation of human Syx, a RhoGEF implicated in glioblastoma.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2022Article
- In vitro fluorescence assay to measure GDP/GTP exchange of guanine nucleotide exchange factors of Rho family GTPases.Biology methods & protocols · 2022Article
- BRAG1/IQSEC2 as a regulator of small GTPase-dependent trafficking.Small GTPases · 2020Review
- Interaction of the N terminus of ADP-ribosylation factor with the PH domain of the GTPase-activating protein ASAP1 requires phosphatidylinositol 4,5-bisphosphate.The Journal of biological chemistry · 2019Article
- ARF GTPases and their GEFs and GAPs: concepts and challenges.Molecular biology of the cell · 2019Review
- PH-domain-binding inhibitors of nucleotide exchange factor BRAG2 disrupt Arf GTPase signaling.Nature chemical biology · 2019Article
- Multiple interactions between an Arf/GEF complex and charged lipids determine activation kinetics on the membrane.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- Quantifying lipid changes in various membrane compartments using lipid binding protein domains.Cell calcium · 2017Review
- Using HHsearch to tackle proteins of unknown function: A pilot study with PH domains.Traffic (Copenhagen, Denmark) · 2016Article
- The BRAG/IQSec family of Arf GEFs.Small GTPases · 2016Review
- Allosteric regulation of Arf GTPases and their GEFs at the membrane interface.Small GTPases · 2016Review
- Inhibition of Cytohesins Protects against Genetic Models of Motor Neuron Disease.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2015Article
- Polyphosphoinositide binding domains: Key to inositol lipid biology.Biochimica et biophysica acta · 2015Review
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Authors and funding
4 authors at 3 institutions in 1 country.
Funding
Abstract
Brag2, a Sec7 domain (sec7d)-containing guanine nucleotide exchange factor, regulates cell adhesion and tumor cell invasion. Brag2 catalyzes nucleotide exchange, converting Arf·GDP to Arf·GTP. Brag2 contains a pleckstrin homology (PH) domain, and its nucleotide exchange activity is stimulated by phosphatidylinositol 4,5-bisphosphate (PIP(2)). Here we determined kinetic parameters for Brag2 and examined the basis for regulation by phosphoinositides. Using myristoylated Arf1·GDP as a substrate, the k(cat) was 1.8 ± 0.1/s as determined by single turnover kinetics, and the K(m) was 0.20 ± 0.07 μm as determined by substrate saturation kinetics. PIP(2) decreased the K(m) and increased the k(cat) of the reaction. The effect of PIP(2) required the PH domain of Brag2 and the N terminus of Arf and was largely independent of Arf myristoylation. Structural analysis indicated that the linker between the sec7d and the PH domain in Brag2 may directly contact Arf. In support, we found that a Brag2 fragment containing the sec7d and the linker was more active than sec7d alone. We conclude that Brag2 is allosterically regulated by PIP(2) binding to the PH domain and that activity depends on the interdomain linker. Thus, the PH domain and the interdomain linker of Brag2 may be targets for selectively regulating the activity of Brag2.
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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 OpenQuestion graph.