HGNC Approved Gene Symbol: RALGDS
Cytogenetic location: 9q34.13-q34.2 Genomic coordinates (GRCh38): 9:133,097,722-133,149,210 (from NCBI)
Guanine nucleotide dissociation stimulators (GDSs, or exchange factors), such as RALGDS, are effectors of Ras-related GTPases (see 190020) that participate in signaling for a variety of cellular processes.
Albright et al. (1993) used sequences derived from the yeast rasGDS proteins as probes and cloned cDNAs encoding a novel murine GDS protein. The protein stimulated the dissociation of guanine nucleotides from the ralA (179550) and ralB (179551) GTPases. The protein, designated RalGDS by them, was at least 20-fold more active on the ralA and ralB GTPases than any other GTPases tested. The 3.6-kb ralGDS mRNA and the 115-kD ralGDS protein were found in all tissues examined.
Hofer et al. (1994) used a yeast 2-hybrid system to identify proteins in human that interact with Ras and isolated a gene encoding RALGDS, a protein which had previously been identified in mouse by Albright et al. (1993) as a guanine nucleotide exchange factor for the Ras-like molecule Ral.
Hofer et al. (1994) reported that the interaction with Ras and Ras-like molecules was mediated by the C-terminal noncatalytic segment of RALGDS. They demonstrated that the interaction of the RALGDS C-terminal region with Ras is specific and dependent on the activation of Ras by GTP.
Spaargaren and Bischoff (1994) used a yeast 2-hybrid system to screen for proteins that bind to RRAS (165090). From this screen they obtained several clones that encoded the C-terminal region of the guanine nucleotide dissociation stimulator for Ral (RALGDS). Using the 2-hybrid system Spaargaren and Bischoff (1994) showed that the RRAS-binding domain of RALGDS interacts with HRAS, KRAS (190070), and Rap (RAP1A; 179520). Their data further indicated that RALGDS is a putative effector molecule for RRAS, HRAS, KRAS, and Rap.
Urano et al. (1996) demonstrated that ras-H (Hras), Rras, and Rap1A have the capacity to bind RalGDS in mammalian cells; however, only Hras activated RalGDS. From these and other data they concluded that activation of RalGDS and its target Ral constitutes a distinct downstream signaling pathway from Hras that potentiates oncogenic transformation.
Schuler et al. (1996) generated a map of the human genome facilitated by the availability of expressed sequence tags (ESTs) mapping to radiation hybrid panels. Based on sequence similarity to an EST (GenBank stsG2452), Schuler et al. (1996) tentatively mapped the RALGDS gene to chromosome 9q34.
Albright, C. F., Giddings, B. W., Liu, J., Vito, M., Weinberg, R. A. Characterization of a guanine nucleotide dissociation stimulator for a ras-related GTPase. EMBO J. 12: 339-347, 1993. [PubMed: 8094051] [Full Text: https://doi.org/10.1002/j.1460-2075.1993.tb05662.x]
Hofer, F., Fields, S., Schneider, C., Martin, G. S. Activated Ras interacts with the Ral guanine nucleotide dissociation stimulator. Proc. Nat. Acad. Sci. 91: 11089-11093, 1994. [PubMed: 7972015] [Full Text: https://doi.org/10.1073/pnas.91.23.11089]
Schuler, G. D., Boguski, M. S., Stewart, E. A., Stein, L. D., Gyapay, G., Rice, K., White, R. E., Rodriguez-Tome, P., Aggarwal, A., Bajorek, E., Bentolila, S., Birren, B. B., Butler, A., Castle, A. B., Chiannilkulchai, N., Chu, A., Clee, C., Cowles, S., Day, P. J. R., Dibling, T., and 84 others. A gene map of the human genome. Science 274: 540-546, 1996. [PubMed: 8849440]
Spaargaren, M., Bischoff, J. R. Identification of the guanine nucleotide dissociation stimulator for Ral as a putative effector molecule of R-ras, H-ras, K-ras, and Rap. Proc. Nat. Acad. Sci. 91: 12609-12613, 1994. [PubMed: 7809086] [Full Text: https://doi.org/10.1073/pnas.91.26.12609]
Urano, T., Emkey, R., Feig, L. A. Ral-GTPases mediate a distinct downstream signaling pathway from Ras that facilitates cellular transformation. EMBO J. 15: 810-816, 1996. [PubMed: 8631302]