The DOI matches its Crossref record; 37 of the 37 references it cites were found in a registry or an index.
Identification and Characterization of RA-GEF-2, a Rap Guanine Nucleotide Exchange Factor That Serves as a Downstream Target of M-Ras
Open accessAbstract
The Ras family small GTPase Rap is regulated by an array of specific guanine nucleotide exchange factors (GEFs) in response to upstream stimuli. RA-GEF-1 was identified as a novel Rap GEF, which possesses a Ras/Rap1-associating (RA) domain. Here we report a protein closely related to RA-GEF-1, named RA-GEF-2. Like RA-GEF-1, a putative cyclic nucleotide monophosphate-binding domain, a Ras exchanger motif, a PSD-95/DlgA/ZO-1 domain, and an RA domain in addition to the GEF catalytic domain are found in RA-GEF-2. However, RA-GEF-2 displays a different tissue distribution profile from that of RA-GEF-1. RA-GEF-2 stimulates guanine nucleotide exchange of both Rap1 and Rap2, but not Ha-Ras. The RA domain of RA-GEF-2 binds to M-Ras in a GTP-dependent manner, but not to other Ras family GTPases tested, including Ha-Ras, N-Ras, Rap1A, Rap2A, R-Ras, RalA, Rin, Rit, and Rheb, in contrast to the RA domain of RA-GEF-1, which specifically binds to Rap1. In accordance with this, RA-GEF-2 colocalizes with activated M-Ras in the plasma membrane in COS-7 cells, suggesting a role of RA-GEF-2 in the regulation of Rap1 and Rap2, particularly in the plasma membrane. In fact, an increase in the level of the GTP-bound form of plasma membrane-located Rap1 was observed when coexpressed with RA-GEF-2 and activated M-Ras. Thus, RA-GEF-2 acts as a GEF for Rap1 and Rap2 downstream of M-Ras in the plasma membrane, whereas RA-GEF-1 exerts Rap GEF function in perinuclear compartments including the Golgi apparatus.
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“This suggests that MRAS may regulate other signaling pathways involving Rho, Ral or Rap GTPases38,53,54, contributing to tumor cell migration adhesion, endocytosis or invasion.”
From Co-targeting SOS1 enhances the antitumor effects of KRASG12C inhibitors by addressing intrinsic and acquired resistance (2024) · cites this paper as [53]
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“it also uniquely associates with SHOC2 and PPI1C40 as well as certain RapGEFs52,53.”
From Co-targeting SOS1 enhances the antitumor effects of KRASG12C inhibitors by addressing intrinsic and acquired resistance (2024) · cites this paper as [53]
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Signaling Through Scaffold, Anchoring, and Adaptor Proteins
Pawson, T., & Scott, J. D. (1997) · Science · doi:10.1126/science.278.5346.2075 · Cited by 2,256
Epac is a Rap1 guanine-nucleotide-exchange factor directly activated by cyclic AMP
de Rooij, J., Zwartkruis, F. J. T., Verheijen, M. H. G., Cool, R. H., Nijman, S. M. B., Wittinghofer, A., & Bos, J. L. (1998) · Nature · doi:10.1038/24884 · Cited by 1,970
pEF-BOS, a powerful mammalian expression vector
Mizushima, S., & Nagata, S. (1990) · Nucleic Acids Research · doi:10.1093/nar/18.17.5322 · Cited by 1,594
A Family of cAMP-Binding Proteins That Directly Activate Rap1
Kawasaki, H., Springett, G. M., Mochizuki, N., Toki, S., Nakaya, M., Matsuda, M., Housman, D. E., & Graybiel, A. M. (1998) · Science · doi:10.1126/science.282.5397.2275 · Cited by 1,386
FUNCTION AND REGULATION OF RAS
Lowy, D. R., & Willumsen, B. M. (1993) · Annual Review of Biochemistry · doi:10.1146/annurev.bi.62.070193.004223 · Cited by 1,164
cAMP Activates MAP Kinase and Elk-1 through a B-Raf- and Rap1-Dependent Pathway
Vossler, M. R., Yao, H. W., York, R. D., Pan, M., Rim, C. S., & Stork, P. A. (1997) · Cell · doi:10.1016/s0092-8674(00)80184-1 · Cited by 1,044
Rap1 mediates sustained MAP kinase activation induced by nerve growth factor
York, R. D., Yao, H. W., Dillon, T. J., Ellig, C. L., Eckert, S. P., McCleskey, E. W., & Stork, P. A. (1998) · Nature · doi:10.1038/33451 · Cited by 858
Rap1 signalling: adhering to new models
Bos, J. L., de Rooij, J., & Reedquist, K. A. (2001) · Nature Reviews Molecular Cell Biology · doi:10.1038/35073073 · Cited by 625
[16] Isolation of subcellular organelles
Storrie, B., & Amadden, E. (1990) · Methods in Enzymology · doi:10.1016/0076-6879(90)82018-w · Cited by 555
Phospholipase Cϵ: a novel Ras effector
Kelley, G. G., Reks, S. E., Ondrako, J. M., & Smrcka, A. V. (2001) · The EMBO Journal · doi:10.1093/emboj/20.4.743 · Cited by 361
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Role of Rap1 in Angiogenesis and Tumor Invasion
Yan, J. (2009) · IUScholarWorks (Indiana University) · doi:10.7912/c2/1852
Thiriet, M. (2012) · Biomathematical and biomechanical modeling of the circulatory and ventilatory systems · doi:10.1007/978-1-4614-4370-4_11
Quilliam, L. A. (2006) · AfCS-Nature Molecule Pages · doi:10.1038/mp.a001038.01
Nussinov, R. (2019) · Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · doi:10.3410/f.735172408.793557246
Ikuta, S., Edamatsu, H., Li, M., Hu, L., & Kataoka, T. (2023) · doi:10.1158/0008-5472.c.6496352.v1
Self-citationNayak, A. P., & Glotzer, M. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.09.21.753314
Metadata
- Authors
- Gao, X., Satoh, T., Liao, Y., Song, C., Hu, C.-D., Kariya, K.-I., & Kataoka, T.
- Affiliations
- Kobe University (JP)
- University of the Ryukyus (JP)
- Corresponding author
- Kataoka, Tohru
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2001-11
- Volume
- 276
- Issue
- 45
- Pages
- 42219-42225
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2003229639
- Cited by
- 106
- References
- 37
- Citations by year
- 2026: 1 · 2024: 2 · 2023: 1 · 2022: 1 · 2020: 2 · 2019: 7 · 2018: 3 · 2017: 4 · 2016: 1 · 2015: 3 · 2014: 2 · 2013: 1 · 2012: 11
- FWCI
- 3.03
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Ministry of Education, Culture, Sports, Science and Technology
- Japan Society for the Promotion of Science
- 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 › Protein Tyrosine Phosphatases
- Keywords
- M-Ras, Rap1, Rap2, plasma membrane localization, Golgi apparatus, tissue distribution
- MeSH terms
- Amino Acid Sequence, Animals, Biological Transport, Cell Membrane, Cloning, Molecular, Molecular Sequence Data, Protozoan Proteins, COS Cells, Monomeric GTP-Binding Proteins, Guanine Nucleotide Exchange Factors
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