Ral GTPases: crucial mediators of exocytosis and tumourigenesis
Abstract
The Ral guanosine triphosphatases (GTPases), RalA and RalB, are members of the Ras superfamily of small GTPases. Research on Ral GTPases and their functions over the past 25 years has revealed the essential involvement of these GTPases in unique and diverse cellular processes including exocyst-mediated exocytosis and related cellular activities. Moreover, it is increasingly appreciated that the aberrant activation of Ral GTPases is one of the major causes of human tumourigenesis induced by oncogenic Ras. Recent evidence suggests that Ral signalling pathways may be potential therapeutic targets for the treatment of human cancers. This review summarizes recent advance in the investigation of Ral GTPases.
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Ral proteins function as molecular switches, cycling between an active GTP-bound state and an inactive GDP-bound state to mediate their biological effects.
“Ral proteins function as molecular switches, cycling between an active guanosine triphosphate (GTP)-bound state and an inactive guanosine diphosphate (GDP)-bound state to mediate their biological effects.”
From Dietary cholesterol activates a Ral-dependent pathway driving LDLR turnover (2026) · cites this paper as [15]
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 [15]
Ral and Rab GTPases cycle between GDP-bound inactive and GTP-bound active states.
“Similar to other small GTPases, Ral and Rab cycle between a guanosine diphosphate (GDP)–bound inactive state and a GTP-bound active state (10–12).”
From Regulation of cargo exocytosis by a Reps1-Ralbp1-RalA module (2023) · cites this paper as [11]
Ralbp1 binds to RalA.
“Ralbp1 binds to RalA, a small GTPase regulating vesicle tethering and fusion through interacting with exocyst (11, 20, 41–44).”
From Regulation of cargo exocytosis by a Reps1-Ralbp1-RalA module (2023) · cites this paper as [11]
RalA regulates vesicle tethering and fusion through interacting with exocyst.
“Ralbp1 binds to RalA, a small GTPase regulating vesicle tethering and fusion through interacting with exocyst (11, 20, 41–44).”
From Regulation of cargo exocytosis by a Reps1-Ralbp1-RalA module (2023) · cites this paper as [11]
The Reps1-Ralbp1-RalA module constitutes an integral segment of the Ral-dependent exocytic pathway, which operates in parallel with the Rab-dependent pathway in mediating cargo exocytosis and maintaining surface protein homeostasis.
“The Reps1-Ralbp1-RalA module constitutes an integral segment of the Ral-dependent exocytic pathway, which operates in parallel with the Rab-dependent pathway in mediating cargo exocytosis and maintaining surface protein homeostasis (11, 59).”
From Regulation of cargo exocytosis by a Reps1-Ralbp1-RalA module (2023) · cites this paper as [11]
Cites
K-Ras(G12C) inhibitors allosterically control GTP affinity and effector interactions
Ostrem, J. M., Peters, U., Sos, M. L., Wells, J. A., & Shokat, K. M. (2013) · Nature · doi:10.1038/nature12796 · Cited by 2,557 · see citing works
Creation of human tumour cells with defined genetic elements
Hahn, W. C., Counter, C. M., Lundberg, A. S., Beijersbergen, R. L., Brooks, M. W., & Weinberg, R. A. (1999) · Nature · doi:10.1038/22780 · Cited by 2,345 · see citing works
The Tuberous Sclerosis Complex
Crino, P. B., Nathanson, K. L., & Henske, E. P. (2006) · New England Journal of Medicine · doi:10.1056/nejmra055323 · Cited by 1,793 · see citing works
M-Sec promotes membrane nanotube formation by interacting with Ral and the exocyst complex
Hase, K., Kimura, S., Takatsu, H., Ohmae, M., Kawano, S., Kitamura, H., Ito, M., Watarai, H., Hazelett, C. C., Yeaman, C., et al. (2009) · Nature Cell Biology · doi:10.1038/ncb1990 · Cited by 402 · see citing works
Discovery and characterization of small molecules that target the GTPase Ral
Yan, C., Liu, D., Li, L., Wempe, M. F., Guin, S., Khanna, M., Meier, J., Hoffman, B., Owens, C., Wysoczynski, C. L., et al. (2014) · Nature · doi:10.1038/nature13713 · Cited by 150 · see citing works
The Rap–RapGAP complex: GTP hydrolysis without catalytic glutamine and arginine residues
Scrima, A., Thomas, C., Deaconescu, D., & Wittinghofer, A. (2008) · The EMBO Journal · doi:10.1038/emboj.2008.30 · Cited by 127 · see citing works
Ral mediates activity‐dependent growth of postsynaptic membranes via recruitment of the exocyst
Teodoro, R. O., Pekkurnaz, G., Nasser, A., Higashi‐Kovtun, M. E., Balakireva, M., McLachlan, I. G., Camonis, J., & Schwarz, T. L. (2013) · The EMBO Journal · doi:10.1038/emboj.2013.147 · Cited by 61 · see citing works
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Ruvolo, P. P. (2016) · BBA Clinical · doi:10.1016/j.bbacli.2016.08.002 · Cited by 143 · see citing works
Regulation of cargo exocytosis by a Reps1-Ralbp1-RalA module
Wang, S., Chen, X., Crisman, L., Dou, X., Winborn, C. S., Wan, C., Puscher, H., Yin, Q., Kennedy, M. J., & Shen, J. (2023) · Science Advances · doi:10.1126/sciadv.ade2540 · Cited by 14 · see citing works
Dietary cholesterol activates a Ral-dependent pathway driving LDLR turnover
Feng, X., Zhang, S., Wang, Y., Kurlagunda, T., Sit, A., Jaishankar, P., Yang, P., Sakane, S., Park, S. Y., Wisessaowapak, C., et al. (2026) · Nature · doi:10.1038/s41586-026-10697-z · Cited by 2 · see citing works
- Authors
- Shirakawa, R., & Horiuchi, H.
- Affiliations
- Tohoku University (JP)
- Institute of Development, Aging and Cancer, Tohoku University (JP)
- Corresponding author
- Shirakawa, R.
- Venue
- Journal of Biochemistry
- Publisher
- Oxford University Press (OUP)
- Published
- 2015-03-20
- Volume
- 157
- Issue
- 5
- Pages
- 285-299
- ISSN
- 0021-924X (ISSN-L)
- OpenAlex
- W2145257181
- Cited by
- 76
- References
- 7
- Citations by year
- 2026: 6 · 2025: 7 · 2024: 1 · 2023: 4 · 2022: 7 · 2021: 11 · 2020: 8 · 2019: 6 · 2018: 4 · 2017: 9 · 2016: 6 · 2015: 7
- FWCI
- 0.84
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Biochemistry (publishedVersion)
- PubMed (publishedVersion)
- HighWire Press Open Archive (submittedVersion)
- Funders
- Ministry of Education, Culture, Sports, Science and Technology
- Japan Society for the Promotion of Science (25290041, 26860181)
- 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 › Extracellular vesicles in disease
- Keywords
- Ral GTPase, RalA, RalB, Ras superfamily, exocytosis, exocyst, tumourigenesis, oncogenic Ras, cancer therapy targets
- MeSH terms
- Animals, Exocytosis, Humans, ral GTP-Binding Proteins, Carcinogenesis
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