Ask about this productRelated genes to: RALGDS Blocking Peptide
- Gene:
- RALGDS NIH gene
- Name:
- ral guanine nucleotide dissociation stimulator
- Previous symbol:
- -
- Synonyms:
- RGF, RalGEF, RGDS
- Chromosome:
- 9q34.13-q34.2
- Locus Type:
- gene with protein product
- Date approved:
- 1997-01-20
- Date modifiied:
- 2018-02-13
Related products to: RALGDS Blocking Peptide
Related articles to: RALGDS Blocking Peptide
- Distinct effector-binding preferences among RAS family GTPases challenge the longstanding view that canonical RAS proteins uniformly bind and activate RAF, PI3Kα, RalGDS, and other downstream effectors. Quantitative binding data, supported by structural insights into effector recognition, instead reveal a division of labor: the canonical RAS subfamily (KRAS, HRAS, NRAS) binds RAF kinases with high affinity, the RRAS subfamily (RRAS2 and MRAS) preferentially engages PI3Kα, and the RAP subfamily (RAP1A and RAP1B) shows the strongest binding to RalGDS. These intrinsic preferences, encoded in the switch regions and further shaped by isoform and effector expression, as well as subcellular localization, establish a hierarchy in which canonical RAS, RRAS2/MRAS, and RAP1A/B primarily activate RAF, PI3Kα, and RalGDS, respectively, in normal cells. Oncogenic mutations at codons G12, G13, or Q61 disrupt this hierarchy by driving sustained accumulation of GTP-bound canonical RAS, enabling engagement of lower-affinity effectors such as PI3Kα and RalGDS. In addition, certain mutations, including KRAS-G12D and -G12V, modestly enhance PI3Kα binding, representing a neomorphic expansion of effector engagement. Together, these effects bypass intrinsic effector selectivity, allowing canonical RAS to co-opt effectors normally associated with other RAS subfamilies and broaden downstream signaling. This framework explains how inherent effector preferences govern normal signaling and how oncogenic mutations override these constraints to expand effector engagement in RAS-driven cancers. - Source: PubMed
Simanshu Dhirendra KMcCormick Frank - M2 macrophages significantly contribute to the advancement of prostate cancer (PCa). This research aims to pinpoint M2 macrophage-associated genes (M2RGs) by leveraging single-cell analyses, with a focus on evaluating their prognostic and therapeutic implications in PCa. - Source: PubMed
Publication date: 2026/02/27
Wu ZhikaiLi JianxinHu JintaoLai CongLi ZhuohangYu HaoYuan ZhihanDai MingzhouShi JuanyiLiu ChengXu Kewei - The Ras subfamily is the most extensively studied branch of the Ras superfamily, with 20% of all human tumors having activating mutations in one of the RAS genes. Recent studies have shown that the Ras/RalGDS/Ral pathway plays a more significant role in the progression of Ras-driven colon and pancreatic cancers than the Ras/Raf and Ras/PI3K pathways. In this study, we investigated the interaction between Ras and the Ras/Rap binding domain (RBD) of RalGDS using long-timescale molecular dynamics simulations. The binding free energy of dimerization showed that Rap1-RBD has the strongest interaction and M-Ras-RBD the weakest interaction among the simulated systems, consistent with experimental results. We noticed that Ras uses the same acidic interface residues when binding to the complementary basic residues of RalGDS and Raf. By analyzing bonding profiles, we identified several conserved interactions across different systems as well as isoform- and mutant-specific preferences. Our results demonstrate that G12D/V mutations favor Glu37-mediated stabilization, specifically through the Glu37-Ser817 hydrogen bond and the Glu37-Tyr815 anion-π interaction. By mapping interface allosteric communication pathways, we illustrated the interplay between these stabilizing interactions and allosteric signal transduction across the dimer. We hypothesize that communication between the Ras active site and the RalGDS RBD is rewired upon G12 mutations. Specifically, we identified the GTP-Gly/Asp/Val12-Gln61-Tyr64-Ile36-Ile803 pathway that exhibits divergent behavior in wild-type versus mutant systems. The interaction dynamics represented here may serve as a good reference point for studies aiming to develop mutant-specific targeting against tumors harboring Ral overactivity. - Source: PubMed
Publication date: 2026/02/17
Demirbas EmirJang HyunbumKosoglu KayraNussinov RuthGursoy AttilaKeskin Ozlem - Systemic sclerosis is an autoimmune rheumatic disorder characterized by uncontrolled fibroblast activation, skin thickening, and fibrosis. Activated Ras and ERK signaling significantly affect fibrosis and EMT upon TGF-β treatment. RalGDS may play an important role in inflammatory and oncogenic processes. This study investigates the expression of RAF and RalGDS genes in SSc patients compared to healthy individuals before and after treatment with TGF-β. - Source: PubMed
Publication date: 2025/11/06
Bakhshi FatemehMahalleh MehrdadKavosi HodaJafarisavari ZahraAhmadzadeh NooshinEnayati SamanehMadreseh ElhamRobat-Jazi BehrouzMahmoudi MahdiFarhadi ElhamVodjgani Mohammad - RAS oncoproteins are the most frequently activated oncoproteins in cancer. Development of direct RAS inhibitors has proved technically challenging and has had limited success in the clinic. Those RAS inhibitors that have been approved tend to suffer from resistance development. Consequently, many attempts have focused on inhibiting RAS indirectly by targeting its immediate downstream effectors. RAS binds and activates three main effector classes to drive transformation: RAF kinases, phosphoinositide 3 (PI-3) kinase and Ras-like (RAL) small GTPases (RALGEF) exchange factors. Multiple FDA-approved inhibitors for RAF and PI-3 kinase exist. So far, they have proved to be of limited effectiveness in patients. However, no inhibitors of the RALGEF effectors with demonstrated antitumor activity have been reported. This is despite the considerable body of evidence supporting a critical role for the RALGEF/RAL pathway in facilitating the in vivo transforming effects of activated RAS. Here, we describe the first small molecule pan-RALGEF inhibitor. We show the inhibitor specifically suppresses RAS/RAL signaling and exhibits antitumor effects in xenograft experiments, including a patient-derived xenograft (pdx) model. This first-in-class compound may lead to the development of more effective therapies for a broad range of RAS-driven tumors. - Source: PubMed
Publication date: 2025/10/08
Donninger HowardFerrill Rachelvon Baby BeccaHobbing Katie RDean William LMiriyala NagarajuJigo RaphaelBurlison JosephTrent John OMonsen RobertClark Geoffrey J