RalGDS RBD Agarose Beads
- Known as:
- RalGDS RBD Agarose Beads
- Catalog number:
- STA-418
- Product Quantity:
- 400
- Category:
- -
- Supplier:
- Cell Biolabs
- Gene target:
- RalGDS RBD Agarose Beads
Related genes to: RalGDS RBD Agarose Beads
- 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 RBD Agarose Beads
Related articles to: RalGDS RBD Agarose Beads
- RAF kinases interpret signals from the three major RAS isoforms to initiate MAPK pathway activation, yet the molecular logic that governs isoform-specific RAS recruitment and the early events that relieve RAF autoinhibition are not yet fully understood. In particular, how the modular N-terminal regulatory architecture of CRAF and ARAF, anchored by the multifunctional cysteine-rich domain (CRD), discriminates among HRAS, KRAS, and NRAS has remained a central unresolved question. Here, we combine quantitative biophysical measurements with structural and dynamic analyses to define how RAS isoform identity and CRD engagement shape the earliest steps of RAF activation. These studies reveal unexpectedly divergent modes of RAS recognition between CRAF and ARAF and expose previously unappreciated functions of the CRD in modulating RAS affinity and intramolecular regulatory contacts. We further identify a direct link between RAS binding and destabilization of RAF autoinhibition, suggesting a mechanism by which RAS engagement facilitates the transition from an inactive monomer to an activation-competent assembly. Finally, we show that emerging KRAS inhibitors variably perturb KRAS-CRAF interactions, offering insight into how these therapeutics influence early RAS-RAF signaling events. Together, this work uncovers distinct biophysical principles that govern RAS-RAF selectivity and reveals a regulatory role for the CRD that reframes our understanding of RAF activation and its dysregulation in RAS-driven cancers. - Source: PubMed
Banerjee ShrheaMalasani SravaniBanerjee ShritiVásquez Maria Celeste LópezMcSorley ShaneWang Zhihong - 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 - BACKGROUND: 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. METHODS: We utilized transcriptomic and scRNA-seq datasets sourced from GEO and TCGA, analyzing both PCa and nearby non-cancerous tissues. M2 macrophage infiltration levels were quantified through “Cibersort” and “xCell” algorithms, followed by assessing their relationship with PCa outcomes. We identified M2RGs using differential expression analysis from scRNA-seq data. A risk score model (M2GS) was subsequently developed using COX and LASSO regression to predict biochemical recurrence-free survival (BRFS) and drug sensitivity. ROC curve analysis and subgroup assessments were conducted to evaluate model performance. Additionally, a nomogram integrating M2GS and clinical parameters was created to refine prediction accuracy. RESULTS: Higher infiltration levels of M2 macrophages were linked to poorer outcomes in patients with prostate cancer (PCa). Using COX regression and LASSO analyses, we identified seven M2 macrophage-related genes (M2RGs) with prognostic significance: MTUS1, NFE2L2, CD9, NOP56, KIF22, RBM3, and RALGDS, which were incorporated into an M2-related gene signature (M2GS). ROC analysis affirmed the model’s predictive capabilities, yielding AUC values of 0.702, 0.752, and 0.831 for predicting 1-, 3-, and 5-year survival, respectively. Subgroup analysis and violin plot comparisons highlighted distinct drug sensitivity patterns between high- and low-risk groups defined by M2GS. Both M2GS and T stage were independently validated as prognostic indicators. The nomogram demonstrated consistent calibration and strong predictive performance. CONCLUSION: Our prognostic risk scoring model effectively predicts BRFS and drug responsiveness in prostate cancer, providing clinicians with valuable guidance for tailoring individualized treatment strategies and follow-up protocols for patients. - 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