ArticleProceedings of the National Academy of Sciences of the United States of America1999
p200 ARF-GEP1: a Golgi-localized guanine nucleotide exchange protein whose Sec7 domain is targeted by the drug brefeldin A.
Article in Proceedings of the National Academy of Sciences of the United States of America, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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Who cites it
47 citing papers in PubMed, 117 citations in OpenAlex.
- BsSYT1 is required for growth, conidiogenesis, stress response and virulence of Bipolaris sorokiniana.World journal of microbiology & biotechnology · 2026Article
- Haploinsufficiency of ARFGEF1 is associated with developmental delay, intellectual disability, and epilepsy with variable expressivity.Genetics in medicine : official journal of the American College of Medical Genetics · 2021Article
- Identification of Genes Required for Apical Protein Trafficking inG3 (Bethesda, Md.) · 2019Article
- BioID Performed on Golgi Enriched Fractions Identify C10orf76 as a GBF1 Binding Protein Essential for Golgi Maintenance and Secretion.Molecular & cellular proteomics : MCP · 2019Article
- Intermediate compartment (IC): from pre-Golgi vacuoles to a semi-autonomous membrane system.Histochemistry and cell biology · 2018Review
- BIG2-ARF1-RhoA-mDia1 Signaling Regulates Dendritic Golgi Polarization in Hippocampal Neurons.Molecular neurobiology · 2018Article
- Highly conserved motifs within the large Sec7 ARF guanine nucleotide exchange factor GBF1 target it to the Golgi and are critical for GBF1 activity.American journal of physiology. Cell physiology · 2018Article
- The HUS box is required for allosteric regulation of the Sec7 Arf-GEF.The Journal of biological chemistry · 2018Article
- Role of curcumin in PLD activation by Arf6-cytohesin1 signaling axis in U46619-stimulated pulmonary artery smooth muscle cells.Molecular and cellular biochemistry · 2018Article
- Article
- Allosteric regulation of Arf GTPases and their GEFs at the membrane interface.Small GTPases · 2016Review
- Structural Insights into Arl1-Mediated Targeting of the Arf-GEF BIG1 to the trans-Golgi.Cell reports · 2016Article
- Oligomerization of the Sec7 domain Arf guanine nucleotide exchange factor GBF1 is dispensable for Golgi localization and function but regulates degradation.American journal of physiology. Cell physiology · 2016Article
- The Sec7 N-terminal regulatory domains facilitate membrane-proximal activation of the Arf1 GTPase.eLife · 2016Article
- Regulating the large Sec7 ARF guanine nucleotide exchange factors: the when, where and how of activation.Cellular and molecular life sciences : CMLS · 2014Review
- Rab4 orchestrates a small GTPase cascade for recruitment of adaptor proteins to early endosomes.Current biology : CB · 2014Article
- Chlamydial intracellular survival strategies.Cold Spring Harbor perspectives in medicine · 2013Review
- The Sec7 guanine nucleotide exchange factor GBF1 regulates membrane recruitment of BIG1 and BIG2 guanine nucleotide exchange factors to the trans-Golgi network (TGN).The Journal of biological chemistry · 2013Article
- The small G protein Arl1 directs the trans-Golgi-specific targeting of the Arf1 exchange factors BIG1 and BIG2.The Journal of cell biology · 2012Article
- Effects of brefeldin A-inhibited guanine nucleotide-exchange (BIG) 1 and KANK1 proteins on cell polarity and directed migration during wound healing.Proceedings of the National Academy of Sciences of the United States of America · 2011Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The drug brefeldin A (BFA) disrupts protein traffic and Golgi morphology by blocking activation of ADP ribosylation factors (ARFs) through an unknown mechanism. Here, we investigated the cellular localization and BFA sensitivity of human p200 ARF-GEP1 (p200), a ubiquitously expressed guanine nucleotide exchange factor of the Sec7 domain family. Multiple tagged forms of the full-length polypeptide localized to tight ribbon-like perinuclear structures that overlapped with the Golgi marker mannosidase II and were distinct from the pattern observed with ERGIC53/58. Analysis of several truncated forms mapped the Golgi-localization signal to the N-terminal third of p200. BFA treatment of transiently or stably transfected cells resulted in the redistribution of Golgi markers and in loss of cell viability, thereby indicating that overproduction of p200 may not be sufficient to overcome the toxic effect. A 39-kDa fragment spanning the Sec7 domain catalyzed loading of guanosine 5'-[gamma-thio]triphosphate onto class I ARFs and displayed clear sensitivity to BFA. Kinetic analysis established that BFA did not compete with ARF for interaction with p200 but, rather, acted as an uncompetitive inhibitor that only targeted the p200-ARF complex with an inhibition constant of 7 microM. On the basis of these results, we propose that accumulation of an abortive p200-ARF complex in the presence of BFA likely leads to disruption of Golgi morphology. p200 mapped to chromosome 8q13, 3.56 centirays from WI-6151, and database searches revealed the presence of putative isoforms whose inhibition may account for the effects of BFA on various organelles.
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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.