SmgGDS is a guanine nucleotide exchange factor that specifically activates RhoA and RhoC
Open accessAbstract
SmgGDS is an atypical guanine nucleotide exchange factor (GEF) that promotes both cell proliferation and migration and is up-regulated in several types of cancer. SmgGDS has been previously shown to activate a wide variety of small GTPases, including the Ras family members Rap1a, Rap1b, and K-Ras, as well as the Rho family members Cdc42, Rac1, Rac2, RhoA, and RhoB. In contrast, here we show that SmgGDS exclusively activates RhoA and RhoC among a large panel of purified GTPases. Consistent with the well known properties of GEFs, this activation is catalytic, and SmgGDS preferentially binds to nucleotide-depleted RhoA relative to either GDP- or GTPγS-bound forms. However, mutational analyses indicate that SmgGDS utilizes a distinct exchange mechanism compared with canonical GEFs and in contrast to known GEFs requires RhoA to retain a polybasic region for activation. A homology model of SmgGDS highlights an electronegative surface patch and a highly conserved binding groove. Mutation of either area ablates the ability of SmgGDS to activate RhoA. Finally, the in vitro specificity of SmgGDS for RhoA and RhoC is retained in cells. Together, these results indicate that SmgGDS is a bona fide GEF that specifically activates RhoA and RhoC through a unique mechanism not used by other Rho family exchange factors.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
SmgGDS specifically activates RhoA and RhoC but not RhoB.
“Another example is SmgGDS, which specifically activates RhoA and RhoC but not RhoB [22].”
From RhoA Signaling in Neurodegenerative Diseases (2022) · cites this paper as [22]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Crystal structure of Rac1 in complex with the guanine nucleotide exchange region of Tiam1
Worthylake, D. K., Rossman, K. L., & Sondek, J. (2000) · Nature · doi:10.1038/35047014 · Cited by 355 · see citing works
Self-citation
Flagged first, then by citations
Research works printed but not linked: 1
- Mizuno, T., Kaibuchi, K., Yamamoto, T., Kawamura, M., Sakoda, T., Fujioka, H., Matsuura, Y., and Takai, Y. (1991) Proc. Natl. Acad. Sci. U.S.A. 88, 6442-6446
Cited by
Sorted by citations
RhoA Signaling in Neurodegenerative Diseases
Schmidt, S. I., Blaabjerg, M., Freude, K., & Meyer, M. (2022) · Cells · doi:10.3390/cells11091520 · Cited by 110 · see citing works
- Authors
- Hamel, B., Monaghan-Benson, E., Rojas, R. J., Temple, B. R. S., Marston, D. J., Burridge, K., & Sondek, J.
- Affiliations
- University of North Carolina at Chapel Hill (US)
- Corresponding author
- Sondek, John
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2011-04
- Volume
- 286
- Issue
- 14
- Pages
- 12141-12148
- ISSN
- 0021-9258 (ISSN-L)
- PMC
- PMC3069418
- OpenAlex
- W2059598052
- Cited by
- 64
- References
- 1
- Citations by year
- 2026: 1 · 2025: 3 · 2023: 5 · 2022: 4 · 2021: 4 · 2020: 7 · 2019: 5 · 2018: 4 · 2017: 3 · 2016: 10 · 2015: 1 · 2014: 6 · 2013: 8 · 2012: 2
- FWCI
- 1.95
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Carolina Digital Repository (University of North Carolina at Chapel Hill) (submittedVersion)
- UNC Libraries
- Funders
- National Institutes of Health (5r01gm062299-08, 5r01gm029860-35, GM029860)
- National Cancer Institute (P30CA016086)
- National Institute of General Medical Sciences (R01-GM062299, R01-GM029860)
- 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 › Cell Biology › Cellular Mechanics and Interactions
- Keywords
- SmgGDS, guanine nucleotide exchange factor, RhoA, RhoC, Rho GTPases, polybasic region, homology model, cancer cell proliferation and migration
- MeSH terms
- Cell Line, Chromatography, Gel, Circular Dichroism, Humans, Protein Binding, Blotting, Western, Protein Structure, Secondary, Protein Structure, Tertiary, Protein Isoforms, Guanine Nucleotide Exchange Factors, rho GTP-Binding Proteins, rhoA GTP-Binding Protein
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
