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Journal articles on the topic 'RalGPS2'

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Author: Grafiati

Published: 9 March 2023

Last updated: 10 March 2023

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1

Tan, Juan, Weimin Wang, Bin Song, Yingjian Song, and Zili Meng. "Integrative Analysis of Three Novel Competing Endogenous RNA Biomarkers with a Prognostic Value in Lung Adenocarcinoma." BioMed Research International 2020 (August 4, 2020): 1–12. http://dx.doi.org/10.1155/2020/2837906.

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Increasing evidence has shown competitive endogenous RNAs (ceRNAs) play key roles in numerous cancers. Nevertheless, the ceRNA network that can predict the prognosis of lung adenocarcinoma (LUAD) is still lacking. The aim of the present study was to identify the prognostic value of key ceRNAs in lung tumorigenesis. Differentially expressed (DE) RNAs were identified between LUAD and adjacent normal samples by limma package in R using The Cancer Genome Atlas database (TCGA). Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway function enrichment analysis was performed using the clusterProfiler package in R. Subsequently, the LUAD ceRNA network was established in three steps based on ceRNA hypothesis. Hub RNAs were identified using degree analysis methods based on Cytoscape plugin cytoHubba. Multivariate Cox regression analysis was implemented to calculate the risk score using the candidate ceRNAs and overall survival information. The survival differences between the high-risk and low-risk ceRNA groups were determined by the Kaplan-Meier and log-rank test using survival and survminer package in R. A total of 2,989 mRNAs, 185 lncRNAs, and 153 miRNAs were identified. GO and KEGG pathway function enrichment analysis showed that DE mRNAs were mainly associated with “sister chromatid segregation,” “regulation of angiogenesis,” “cell adhesion molecules (CAMs),” “cell cycle,” and “ECM-receptor interaction.” LUAD-related ceRNA network was constructed, which comprised of 54 nodes and 78 edges. Top ten hub RNAs (hsa-miR-374a-5p, hsa-miR-374b-5p, hsa-miR-340-5p, hsa-miR-377-3p, hsa-miR-21-5p, hsa-miR-326, SNHG1, RALGPS2, and PITX2) were identified according to their degree. Kaplan-Meier survival analyses demonstrated that hsa-miR-21-5p and RALGPS2 had a significant prognostic value. Finally, we found that a high risk of three novel ceRNA interactions (SNHG1-hsa-miR-21-5p-RALGPS2, SNHG1-hsa-miR-326-RALGPS2, and SNHG1-hsa-miR-377-3p-RALGPS2) was positively associated with worse prognosis. Three novel ceRNAs (SNHG1-hsa-miR-21-5p-RALGPS2, SNHG1-hsa-miR-326-RALGPS2, and SNHG1-hsa-miR-377-3p-RALGPS2) might be potential biomarkers for the prognosis and treatment of LUAD.

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2

D’Aloia, Alessia, Edoardo Arrigoni, Barbara Costa, Giovanna Berruti, Enzo Martegani, Elena Sacco, and Michela Ceriani. "RalGPS2 Interacts with Akt and PDK1 Promoting Tunneling Nanotubes Formation in Bladder Cancer and Kidney Cells Microenvironment." Cancers 13, no. 24 (December 16, 2021): 6330. http://dx.doi.org/10.3390/cancers13246330.

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RalGPS2 is a Ras-independent Guanine Nucleotide Exchange Factor for RalA GTPase that is involved in several cellular processes, including cytoskeletal organization. Previously, we demonstrated that RalGPS2 also plays a role in the formation of tunneling nanotubes (TNTs) in bladder cancer 5637 cells. In particular, TNTs are a novel mechanism of cell–cell communication in the tumor microenvironment, playing a central role in cancer progression and metastasis formation. However, the molecular mechanisms involved in TNTs formation still need to be fully elucidated. Here we demonstrate that mid and high-stage bladder cancer cell lines have functional TNTs, which can transfer mitochondria. Moreover, using confocal fluorescence time-lapse microscopy, we show in 5637 cells that TNTs mediate the trafficking of RalA protein and transmembrane MHC class III protein leukocyte-specific transcript 1 (LST1). Furthermore, we show that RalGPS2 is essential for nanotubes generation, and stress conditions boost its expression both in 5637 and HEK293 cell lines. Finally, we prove that RalGPS2 interacts with Akt and PDK1, in addition to LST1 and RalA, leading to the formation of a complex that promotes nanotubes formation. In conclusion, our findings suggest that in the tumor microenvironment, RalGPS2 orchestrates the assembly of multimolecular complexes that drive the formation of TNTs.

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3

D’Aloia, A., G. Berruti, B. Costa, C. Schiller, R. Ambrosini, V. Pastori, E. Martegani, and M. Ceriani. "RalGPS2 is involved in tunneling nanotubes formation in 5637 bladder cancer cells." Experimental Cell Research 362, no. 2 (January 2018): 349–61. http://dx.doi.org/10.1016/j.yexcr.2017.11.036.

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4

Ceriani, Michela, Cristina Scandiuzzi, Loredana Amigoni, Renata Tisi, Giovanna Berruti, and Enzo Martegani. "Functional analysis of RalGPS2, a murine guanine nucleotide exchange factor for RalA GTPase." Experimental Cell Research 313, no. 11 (July 2007): 2293–307. http://dx.doi.org/10.1016/j.yexcr.2007.03.016.

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5

Ceriani, Michela, Loredana Amigoni, Cristina Scandiuzzi, Giovanna Berruti, and Enzo Martegani. "The PH-PxxP domain of RalGPS2 promotes PC12 cells differentiation acting as a dominant negative for RalA GTPase activation." Neuroscience Research 66, no. 3 (March 2010): 290–98. http://dx.doi.org/10.1016/j.neures.2009.11.013.

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6

O. Santos, Adriana, Maria Carla Parrini, and Jacques Camonis. "RalGPS2 Is Essential for Survival and Cell Cycle Progression of Lung Cancer Cells Independently of Its Established Substrates Ral GTPases." PLOS ONE 11, no. 5 (May 5, 2016): e0154840. http://dx.doi.org/10.1371/journal.pone.0154840.

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7

Guo, Hongjun, Siqiao Wang, Aiqing Xie, Wenhuizi Sun, Chenlu Wei, Shuyuan Xian, Huabin Yin, et al. "Ral GEF with the PH Domain and SH3 Binding Motif 1 Regulated by Splicing Factor Junction Plakoglobin and Pyrimidine Metabolism Are Prognostic in Uterine Carcinosarcoma." Disease Markers 2021 (October 28, 2021): 1–17. http://dx.doi.org/10.1155/2021/1484227.

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Uterine carcinosarcoma (UCS) is a highly invasive malignant tumor that originated from the uterine epithelium. Many studies suggested that the abnormal changes of alternative splicing (AS) of pre-mRNA are related to the occurrence and metastasis of the tumor. This study investigates the mechanism of alternative splicing events (ASEs) in the tumorigenesis and metastasis of UCS. RNA-seq of UCS samples and alternative splicing event (ASE) data of UCS samples were downloaded from The Cancer Genome Atlas (TCGA) and TCGASpliceSeq databases, several times. Firstly, we performed the Cox regression analysis to identify the overall survival-related alternative splicing events (OSRASEs). Secondly, a multivariate model was applied to approach the prognostic values of the risk score. Afterwards, a coexpressed network between splicing factors (SFs) and OSRASEs was constructed. In order to explore the relationship between the potential prognostic signaling pathways and OSRASEs, we fabricated a network between these pathways and OSRASEs. Finally, validations from multidimension platforms were used to explain the results unambiguously. 1,040 OSRASEs were identified by Cox regression. Then, 6 OSRASEs were incorporated in a multivariable model by Lasso regression. The area under the curve (AUC) of the receiver operator characteristic (ROC) curve was 0.957. The risk score rendered from the multivariate model was corroborated to be an independent prognostic factor ( P < 0.001 ). In the network of SFs and ASEs, junction plakoglobin (JUP) noteworthily regulated RALGPS1-87608-AT ( P < 0.001 , R = 0.455 ). Additionally, RALGPS1-87608-AT ( P = 0.006 ) showed a prominent relationship with distant metastasis. KEGG pathways related to prognosis of UCS were selected by gene set variation analysis (GSVA). The pyrimidine metabolism ( P < 0.001 , R = − 0.470 ) was the key pathway coexpressed with RALGPS1. We considered that aberrant JUP significantly regulated RALGPS1-87608-AT and the pyrimidine metabolism pathway might play a significant part in the metastasis and prognosis of UCS.

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8

Kikuchi, A., S. D. Demo, Z. H. Ye, Y. W. Chen, and L. T. Williams. "ralGDS family members interact with the effector loop of ras p21." Molecular and Cellular Biology 14, no. 11 (November 1994): 7483–91. http://dx.doi.org/10.1128/mcb.14.11.7483-7491.1994.

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Using a yeast two-hybrid system, we identified a novel protein which interacts with ras p21. This protein shares 69% amino acid homology with ral guanine nucleotide dissociation stimulator (ralGDS), a GDP/GTP exchange protein for ral p24. We designated this protein RGL, for ralGDS-like. Using the yeast two-hybrid system, we found that an effector loop mutant of ras p21 was defective in interacting with the ras p21-interacting domain of RGL, suggesting that this domain binds to ras p21 through the effector loop of ras p21. Since ralGDS contained a region highly homologous with the ras p21-interacting domain of RGL, we examined whether ralGDS could interact with ras p21. In the yeast two-hybrid system, ralGDS failed to interact with an effector loop mutant of ras p21. In insect cells, ralGDS made a complex with v-ras p21 but not with a dominant negative mutant of ras p21. ralGDS interacted with the GTP-bound form of ras p21 but not with the GDP-bound form in vitro. ralGDS inhibited both the GTPase-activating activity of the neurofibromatosis gene product (NF1) for ras p21 and the interaction of Raf with ras p21 in vitro. These results demonstrate that ralGDS specifically interacts with the active form of ras p21 and that ralGDS can compete with NF1 and Raf for binding to the effector loop of ras p21. Therefore, ralGDS family members may be effector proteins of ras p21 or may inhibit interactions between ras p21 and its effectors.

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9

Kikuchi, A., S. D. Demo, Z. H. Ye, Y. W. Chen, and L. T. Williams. "ralGDS family members interact with the effector loop of ras p21." Molecular and Cellular Biology 14, no. 11 (November 1994): 7483–91. http://dx.doi.org/10.1128/mcb.14.11.7483.

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Using a yeast two-hybrid system, we identified a novel protein which interacts with ras p21. This protein shares 69% amino acid homology with ral guanine nucleotide dissociation stimulator (ralGDS), a GDP/GTP exchange protein for ral p24. We designated this protein RGL, for ralGDS-like. Using the yeast two-hybrid system, we found that an effector loop mutant of ras p21 was defective in interacting with the ras p21-interacting domain of RGL, suggesting that this domain binds to ras p21 through the effector loop of ras p21. Since ralGDS contained a region highly homologous with the ras p21-interacting domain of RGL, we examined whether ralGDS could interact with ras p21. In the yeast two-hybrid system, ralGDS failed to interact with an effector loop mutant of ras p21. In insect cells, ralGDS made a complex with v-ras p21 but not with a dominant negative mutant of ras p21. ralGDS interacted with the GTP-bound form of ras p21 but not with the GDP-bound form in vitro. ralGDS inhibited both the GTPase-activating activity of the neurofibromatosis gene product (NF1) for ras p21 and the interaction of Raf with ras p21 in vitro. These results demonstrate that ralGDS specifically interacts with the active form of ras p21 and that ralGDS can compete with NF1 and Raf for binding to the effector loop of ras p21. Therefore, ralGDS family members may be effector proteins of ras p21 or may inhibit interactions between ras p21 and its effectors.

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10

Rondaij, Mariska G., Ruben Bierings, Ellen L. van Agtmaal, Karina A. Gijzen, Erica Sellink, Astrid Kragt, Stephen S. G. Ferguson, et al. "Guanine exchange factor RalGDS mediates exocytosis of Weibel-Palade bodies from endothelial cells." Blood 112, no. 1 (July 1, 2008): 56–63. http://dx.doi.org/10.1182/blood-2007-07-099309.

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Abstract The small GTP-binding protein Ral has been implicated in regulated exocytosis via its interaction with the mammalian exocyst complex. We have previously demonstrated that Ral is involved in exocytosis of Weibel-Palade bodies (WPBs). Little is known about intracellular signaling pathways that promote activation of Ral in response to ligand binding of G protein–coupled receptors. Here we show that RNAi-mediated knockdown of RalGDS, an exchange factor for Ral, results in inhibition of thrombin- and epinephrine-induced exocytosis of WPBs, while overexpression of RalGDS promotes exocytosis of WPBs. A RalGDS variant lacking its exchange domain behaves in a dominant negative manner by blocking release of WPBs. We also provide evidence that RalGDS binds calmodulin (CaM) via an amino-terminal CaM-binding domain. RalGDS association to CaM is required for Ral activation because a cell-permeable peptide comprising this RalGDS CaM-binding domain inhibits Ral activation and WPB exocytosis. Together our findings suggest that RalGDS plays a vital role in the regulation of Ral-dependent WPB exocytosis after stimulation with Ca2+- or cAMP-raising agonists.

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11

Hao, Yansheng, Richard Wong, and Larry A. Feig. "RalGDS Couples Growth Factor Signaling to Akt Activation." Molecular and Cellular Biology 28, no. 9 (February 19, 2008): 2851–59. http://dx.doi.org/10.1128/mcb.01917-07.

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ABSTRACT The Akt kinase is a key regulator of cell proliferation and survival. It is activated in part by PDK1-induced phosphorylation. Here we show that RalGDS, a Ras effector protein that activates Ral GTPases, has a second function that promotes Akt phosphorylation by PDK1 by bringing these two kinases together. In support of this conclusion is our finding that suppression of RalGDS expression in cells inhibits both epidermal growth factor and insulin-induced phosphorylation of Akt. Moreover, while PDK1 complexes with N-GDS, Akt complexes with the central region of RalGDS through an intermediary, JIP1. The biological significance of this newly discovered RalGDS function is highlighted by the observation that an N-terminally deleted mutant of RalGDS that retains the ability to activate Ral proteins but loses the ability to activate Akt also fails to promote cell proliferation. Thus, RalGDS forms a nexus that transduces growth factor signaling to both Ral GTPase and Akt-mediated signaling cascades.

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12

Voorberg, Jan, Mariska G. Rondaij, Karina A. Gijzen, Ruben Bierings, Erica Sellink, Mar Fernandez-Borja, and Jan A. van Mourik. "The Guanine Exchange Factor RalGDS Is Involved in Regulated Exocytosis of Weibel-Palade Bodies from Endothelial Cells." Blood 106, no. 11 (November 16, 2005): 3688. http://dx.doi.org/10.1182/blood.v106.11.3688.3688.

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Abstract Endothelial cells contribute to vascular homeostasis and mediate pathophysiological responses to hypoxia-induced injury and inflammatory events. To ensure rapid responses to vascular perturbation endothelial cells contain intracellular storage pools for inflammatory mediators and pro-thrombotic compounds. One of the best characterized storage granules within endothelial cells are the Weibel-Palade bodies (WPB), rod-shaped organelles that contains P-selectin, Von Willebrand Factor (VWF), interleukin-8 (IL-8) and a number of other proteins with diverse biological activities. Agonist-induced triggering of heterotrimeric G protein coupled receptors (GPCR) present on endothelial cells promote exocytosis of WPB. We have previously shown that the small GTP binding protein RalA is involved in thrombin induced exocytosis of Weibel-Palade bodies. Exocytosis of Weibel-Palade bodies was found to coincide with the activation of RalA in response to thrombin. More recently, we have shown that cAMP-raising stimuli such as epinephrine also coincide with the activation of RalA. Consistent with these findings constitutively active RalG23V was capable of inducing release of WPB from endothelial cells. Small GTPases are activated by guanine exchange factors (GEFs) that induce GDP release thereby enhancing GTP binding to the small GTPase. RalGDS is a widely expressed GEF for Ral that has recently been implicated in cytoskeletal rearrangements that result from activation of GPCRs. Here, we investigated whether RalGDS is involved in thrombin- and/or epinephrine-induced exocytosis of WPB from endothelial cells. First, we showed by RT-PCR that human endothelial cells express RalGDS. Overexpression of a GFP-tagged variant of RalGDS in endothelial cells reduces the number of WPB in endothelial cells suggesting that RalGDS can promote exocytosis of these subcellular organelles. To investigate whether endogenously synthesized RalGDS plays a role in exocytosis of WPBs we designed short hairpin RNAs that acts as small interfering RNA (siRNA). Co-expression of siRalGDS and GFP-RalGDS in heterologously transfected 293 cells markedly reduced expression levels of GFP-RalGDS. Subsequently, we addressed the effect of siRalGDS on exocytosis of WPB in endothelial cells. Knockdown of endogenous RalGDS using siRNA prevented thrombin-induced release of WPBs. Expression of siRalGDS also interfered with WPB release in response to epinephrine. These results show that knock down of RalGDS interferes with exocytosis of WPB in endothelial cells. A dominant negative RalGDS variant, RalGDSΔGEF, lacking its catalytic exchange domain, was subsequently introduced in endothelial cells. As expected, no release of WPB was observed in endothelial cells expressing RalGDSΔGEF. Remarkably, both thrombin- and epinephrine-induced exocytosis were impaired in cells expressing RalGDSΔGEF. Together, these findings indicate that the Ral-specific guanine exchange factor RalGDS is involved in exocytosis of WPB from endothelial cells.

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13

Gao, P., S. Liu, R. Yoshida, C. Y. Shi, S. Yoshimachi, N. Sakata, K. Goto, et al. "Ral GTPase Activation by Downregulation of RalGAP Enhances Oral Squamous Cell Carcinoma Progression." Journal of Dental Research 98, no. 9 (July 22, 2019): 1011–19. http://dx.doi.org/10.1177/0022034519860828.

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Ral small GTPases, consisting of RalA and RalB, are members of the Ras family. Their activity is upregulated by RalGEFs. Since several RalGEFs are downstream effectors of Ras, Ral is activated by the oncogenic mutant Ras. Ral is negatively regulated by RalGAP complexes that consist of a catalytic α1 or α2 subunit and its common partner β subunit and similarly regulate the activity of RalA as well as RalB in vitro. Ral plays an important role in the formation and progression of pancreatic and lung cancers. However, the involvement of Ral in oral squamous cell carcinoma (OSCC) is unclear. In this study, we investigated OSCC by focusing on Ral. OSCC cell lines with high Ral activation exhibited higher motility. We showed that knockdown of RalGAPβ increased the activation level of RalA and promoted the migration and invasion of HSC-2 OSCC cells in vitro. In contrast, overexpression of wild-type RalGAPα2 in TSU OSCC cells attenuated the activation level of RalA and inhibited cell migration and invasion. Real-time quantitative polymerase chain reaction analysis of samples from patients with OSCC showed that RalGAPα2 was downregulated in oral cancer tissues as compared with normal epithelia. Among patients with OSCC, those with a lower expression of RalGAPα2 showed a worse overall survival rate. A comparison of DNA methylation and histone modifications of the RalGAPα2 gene in OSCC cell lines suggested that crosstalk among DNA methylation, histone H4Ac, and H3K27me2 was involved in the downregulation of RalGAPα2. Thus, activation of Ral GTPase by downregulation of RalGAP expression via a potential epigenetic mechanism may enhance OSCC progression.

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14

Ferro, Elisa, David Magrini, Paolo Guazzi, Thomas H. Fischer, Sara Pistolesi, Rebecca Pogni, Gilbert C. White, and Lorenza Trabalzini. "G-protein binding features and regulation of the RalGDS family member, RGL2." Biochemical Journal 415, no. 1 (September 12, 2008): 145–54. http://dx.doi.org/10.1042/bj20080255.

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RGL2 [RalGDS (Ral guanine nucleotide dissociation stimulator)-like 2] is a member of the RalGDS family that we have previously isolated and characterized as a potential effector for Ras and the Ras analogue Rap1b. The protein shares 89% sequence identity with its mouse orthologue Rlf (RalGDS-like factor). In the present study we further characterized the G-protein-binding features of RGL2 and also demonstrated that RGL2 has guanine-nucleotide-exchange activity toward the small GTPase RalA. We found that RGL2/Rlf properties are well conserved between human and mouse species. Both RGL2 and Rlf have a putative PKA (protein kinase A) phosphorylation site at the C-terminal of the domain that regulates the interaction with small GTPases. We demonstrated that RGL2 is phosphorylated by PKA and phosphorylation reduces the ability of RGL2 to bind H-Ras. As RGL2 and Rlf are unique in the RalGDS family in having a PKA site in the Ras-binding domain, the results of the present study indicate that Ras may distinguish between the different RalGDS family members by their phosphorylation by PKA.

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15

Rodriguez-Viciana, Pablo, and Frank McCormick. "RalGDS comes of age." Cancer Cell 7, no. 3 (March 2005): 205–6. http://dx.doi.org/10.1016/j.ccr.2005.02.012.

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16

Johnson, Sandra A. S., Nihar Mandavia, Horng-Dar Wang, and Deborah L. Johnson. "Transcriptional Regulation of the TATA-Binding Protein by Ras Cellular Signaling." Molecular and Cellular Biology 20, no. 14 (July 15, 2000): 5000–5009. http://dx.doi.org/10.1128/mcb.20.14.5000-5009.2000.

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ABSTRACT Our previous studies have demonstrated that the level of the central transcription factor TATA-binding protein (TBP) is increased in cells expressing the hepatitis B virus (HBV) X protein through the activation of the Ras signaling pathway, which serves to enhance both RNA polymerase I and III promoter activities. To understand the mechanism by which TBP is regulated, we have investigated whether enhanced expression is modulated at the transcriptional level. Nuclear run-on assays revealed that the HBV X protein increases the number of active transcription complexes on the TBP gene. In transient-transfection assays with both transformed and primary hepatocytes, the human TBP promoter was shown to be induced by expression of the HBV X protein in a Ras-dependent manner, requiring both Ral guanine nucleotide dissociation stimulator (RalGDS) and Raf signaling. Transient overexpression of TBP did not affect TBP promoter activity. To further delineate the downstream Ras-mediated events contributing to TBP promoter regulation in primary rat hepatocytes, the best-characterized Ras effectors, Raf, phosphoinositide 3-kinase (PI-3 kinase), and RalGDS, were examined. Activation of either Raf or RalGDS, but not that of PI-3 kinase, was sufficient to induce TBP promoter activity. Both Raf- and RalGDS-mediated induction required the activation of mitogen-activated protein kinase kinase (MEK). In addition, another distinct Ras-activated pathway, which does not require MEK activation, appears to induce TBP promoter activity. Analysis of the DNA sequence requirement within the TBP promoter responsible for these regulatory events defined three distinct regions that modulate the abilities of Raf, RalGDS, and the Ras-dependent, MEK-independent pathways to regulate human TBP promoter activity. Together, these results provide new evidence that TBP can be regulated at the transcriptional level and identify three distinct Ras-activated pathways that modulate this central eukaryotic transcription factor.

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17

Liao, Shenling, He He, Yuping Zeng, Lidan Yang, Zhi Liu, Zhenmei An, and Mei Zhang. "A nomogram for predicting metabolic steatohepatitis: The combination of NAMPT, RALGDS, GADD45B, FOSL2, RTP3, and RASD1." Open Medicine 16, no. 1 (January 1, 2021): 773–85. http://dx.doi.org/10.1515/med-2021-0286.

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Abstract Objective To identify differentially expressed and clinically significant mRNAs and construct a potential prediction model for metabolic steatohepatitis (MASH). Method We downloaded four microarray datasets, GSE89632, GSE24807, GSE63067, and GSE48452, from the Gene Expression Omnibus database. The differentially expressed genes (DEGs) analysis and weighted gene co-expression network analysis were performed to screen significant genes. Finally, we constructed a nomogram of six hub genes in predicting MASH and assessed it through receiver operating characteristic (ROC) curve, calibration plot, and decision curve analysis (DCA). In addition, qRT-PCR was used for relative quantitative detection of RNA in QSG-7011 cells to further verify the expression of the selected mRNA in fatty liver cells. Results Based on common DEGs and brown and yellow modules, seven hub genes were identified, which were NAMPT, PHLDA1, RALGDS, GADD45B, FOSL2, RTP3, and RASD1. After logistic regression analysis, six hub genes were used to establish the nomogram, which were NAMPT, RALGDS, GADD45B, FOSL2, RTP3, and RASD1. The area under the ROC of the nomogram was 0.897. The DCA showed that when the threshold probability of MASH was 0–0.8, the prediction model was valuable to GSE48452. In QSG-7011 fatty liver model cells, the relative expression levels of NAMPT, GADD45B, FOSL2, RTP3, RASD1 and RALGDS were lower than the control group. Conclusion We identified seven hub genes NAMPT, PHLDA1, RALGDS, GADD45B, FOSL2, RTP3, and RASD1. The nomogram showed good performance in the prediction of MASH and it had clinical utility in distinguishing MASH from simple steatosis.

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Trojani, Alessandra, Antonino Greco, Alessandra Tedeschi, Barbara Di Camillo, Milena Lodola, Francesca Ricci, Mauro Turrini, Marzia Varettoni, Sara Rattotti, and Enrica Morra. "Microarray Identifies Different Molecular Signatures of Waldenstrom Macroglobulinemia (WM) Compared to IgM Monoclonal Gammopathy of Undetermined Significance (IgMMGUS)." Blood 120, no. 21 (November 16, 2012): 3495. http://dx.doi.org/10.1182/blood.v120.21.3495.3495.

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Abstract Abstract 3495 WM is a rare malignant B-cell disorder characterized by lymphoplasmacytic infiltration of the bone marrow (BM) and hypersecretion of monoclonal IgM. IgMMGUS is an asymptomatic condition characterized by the presence of a serum monoclonal IgM protein and bone marrow infiltration < 10%. WM (symptomatic and indolent) and IgMMGUS can be identified based on two main features, the bone marrow infiltration and the existence of signs and symptoms. The biological and genetic characteristics of both conditions need to be explored. Our study aims to highlight the different expression profiles between WM and IgMMGUS comparing CD19+ as well as CD138+ cells. We have investigated patients with WM (n =21) and patients affected by IgMMGUS (n=10). BM CD19+ and BM CD138+ cells were isolated from 21 WM patients, while BM CD19+ and BM CD138+ were isolated from 10 and 4 IgMMGUS patients, respectively. Microarray analysis was performed using Affymetrix GeneChip Human Genome U133 Plus 2.0 Array. Data was preprocessed using Robust Multi-Array Average (RMA) software. Differential expression analysis was performed using Significant Analysis of Microarrays (SAM). Genes showing a q value lower than 5% and an absolute fold change greater than 2 were selected for further clustering analysis which was performed applying complete linkage hierarchical agglomerative clustering on Euclidean pairwise distances between genes. Microarray of WM vs IgMMGUS CD19+ cells has highlighted 151 differently expressed genes (Fig. 1). Among them we have found 33 genes involved in the regulation of transcription which were significantly overexpressed in WM vs. IgMMGUS. BM WM CD19+ cells overexpressed the following 14 Zinc Finger Protein (ZNF) genes: ZBTB40, ZNF83, ZNF137P, ZNF177, ZNF224, ZNF264, ZNF320, ZNF395, ZNF514, ZNF532, ZNF623, ZNF767, ZNF785, ZNF850. Other genes acting as regulators of transcription overexpressed in WM B cells were: HIF1AN, BHLHE41, EZH1, CCNL2, TCFL5, BLZF1, CIITA, PER2, MECP2, PRDM2, and ELP2. In particular, HIF1AN belongs to the PI3K/Akt/mTOR pathway, ELP2 is involved in the JAK/STAT process, and BHLHE41 and PER2 are included in the cicardian clock showing that these different biological mechanisms differently develop in WM with respect to IgMMGUS. TNFRSF10A, MAP4K4, TNFRSF10B, WNK1, DUSP22, ITPKB genes were overexpressed in WM B cells showing the involvement of Akt and MAPK signaling pathways which can play an important role in WM cells as they regulate several biological processes including cell growth, differentiation, survival, migration and metabolism. Gene expression profiling across CD138+ cells have demonstrated 43 differently expressed genes between WM vs. IgMMGUS (Fig. 2). MS4A1, BANK1 genes were overexpressed with high fold changes (FC) of 11.6 and 9.4, respectively, as well as GPR183, SWAP70 which were significantly overexpressed in WM vs. IGMMGUS, both genes showing a FC of 5. These results suggest that B cell activation and immune response are biological processes which act differently in WM compared to IgMMGUS. RALGPS2(FC=4), PLEKHG1 (FC=10) and ARHGAP24 (FC=4) genes mediating GTPase regulator activity of signal transduction were overexpressed in WM. ARHGAP24 could also be involved in the modulation of angiogenesis. FCRL2 and FCRLA genes involved in cell-cell signaling and cell differentiation, were significantly overexpressed in WM vs. IgMMGUS CD138+ with a fold change of 4.6 and 9, respectively. Again, the immune response seems to be a biological mechanism involved in WM CD138+ cells as CD79B (FC=5) and HLA-DOA (FC=4) genes were overexpressed in WM in respect to IgMMGUS. These differences may reflect varied immune mechanisms in the two disorders. In conclusion, the regulation of transcription, PI3K/Akt/mTOR and MAPK signaling pathways are the most relevant gene ontology biological processes occurring in CD19+ cells, while immune response, cell activation and signaling processes developing in CD138+ cells mainly distinguish WM and IgMMGUS. Future studies of the biological role of the genes differently expressed in WM vs IgMMGUS could clarify the pathogenetic processes underlying IgMMGUS and WM. The understanding of the molecular mechanisms leading to the progression of IgMMGUS to WM could help the identification of IgMMGUS patients who are at high risk for progression to WM. Fig. 1 GEP of BM WM CD19+ cells vs. IgMMGUS CD19+ cells. Fig. 1. GEP of BM WM CD19+ cells vs. IgMMGUS CD19+ cells. Fig. 2 GEP of BM WM CD138+ cells vs. IgMMGUS CD138+ cells. Fig. 2. GEP of BM WM CD138+ cells vs. IgMMGUS CD138+ cells. Disclosures: No relevant conflicts of interest to declare.

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Omholt, Katarina, and Johan Hansson. "No evidence of RALGDS mutations in cutaneous melanoma." Melanoma Research 17, no. 6 (December 2007): 410–12. http://dx.doi.org/10.1097/cmr.0b013e3282ef4178.

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Cassani, Barbara. "RalGAPα2 and NLRP3 Orchestrate Tumor Invasion in Colitis-Associated Cancers." Cellular and Molecular Gastroenterology and Hepatology 9, no. 2 (2020): 339–40. http://dx.doi.org/10.1016/j.jcmgh.2019.11.004.

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Miller, Marsha J., Sally Prigent, Erik Kupperman, Lise Rioux, Sang-Ho Park, James R. Feramisco, Michael A. White, J. Lynn Rutkowski, and Judy L. Meinkoth. "RalGDS Functions in Ras- and cAMP-mediated Growth Stimulation." Journal of Biological Chemistry 272, no. 9 (February 28, 1997): 5600–5605. http://dx.doi.org/10.1074/jbc.272.9.5600.

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Vetter, I. R., T. Linnemann, S. Wohlgemuth, M. Geyer, H. R. Kalbitzer, C. Herrmann, and A. Wittinghofer. "Structural and biochemical analysis of Ras-effector signaling via RalGDS." FEBS Letters 451, no. 2 (May 21, 1999): 175–80. http://dx.doi.org/10.1016/s0014-5793(99)00555-4.

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Huang, Lan, Xiangwei Weng, Franz Hofer, G. Steven Martin, and Sung-Hou Kirn. "Three-dimensional structure of the Ras-interacting domain of RalGDS." Natural Structural Biology 4, no. 8 (August 1997): 609–15. http://dx.doi.org/10.1038/nsb0897-609.

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24

de Bruyn, Kim M. T., Johan de Rooij, Rob M. F. Wolthuis, Holger Rehmann, Joep Wesenbeek, Robbert H. Cool, Alfred H. Wittinghofer, and Johannes L. Bos. "RalGEF2, a Pleckstrin Homology Domain Containing Guanine Nucleotide Exchange Factor for Ral." Journal of Biological Chemistry 275, no. 38 (July 10, 2000): 29761–66. http://dx.doi.org/10.1074/jbc.m001160200.

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25

M’Rabet, Laura, Paul Coffer, Fried Zwartkruis, Barbara Franke, Anthony W. Segal, Leo Koenderman, and Johannes L. Bos. "Activation of the Small GTPase Rap1 in Human Neutrophils." Blood 92, no. 6 (September 15, 1998): 2133–40. http://dx.doi.org/10.1182/blood.v92.6.2133.

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Abstract The small GTPase Rap1 is highly expressed in human neutrophils, but its function is largely unknown. Using the Rap1-binding domain of RalGDS (RalGDS-RBD) as an activation-specific probe for Rap1, we have investigated the regulation of Rap1 activity in primary human neutrophils. We found that a variety of stimuli involved in neutrophil activation, including fMet-Leu-Phe (fMLP), platelet-activating factor (PAF), granulocyte-macrophage colony-stimulating factor (GM-CSF), and IgG-coated particles, induce a rapid and transient Rap1 activation. In addition, we found that Rap1 is normally activated in neutrophils from chronic granulomatous disease patients that lack cytochrome b558 or p47phox and have a defective NADPH oxidase system. From these results we conclude that in neutrophils Rap1 is activated independently of respiratory burst induction. Finally, we found that Rap1 is activated by both the Ca2+ ionophore ionomycin and the phorbol ester 12-O-tetradecanoylphorbol 13-acetate (TPA), indicating that phospholipase C (PLC) activation leading to elevated levels of intracellular free Ca2+ and diacylglycerol (DAG) can mediate Rap1 activation. However, inhibition of PLC and Ca2+ depletion only marginally affected fMLP-induced Rap1 activation, suggesting that additional pathways may control Rap1 activation. © 1998 by The American Society of Hematology.

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M’Rabet, Laura, Paul Coffer, Fried Zwartkruis, Barbara Franke, Anthony W. Segal, Leo Koenderman, and Johannes L. Bos. "Activation of the Small GTPase Rap1 in Human Neutrophils." Blood 92, no. 6 (September 15, 1998): 2133–40. http://dx.doi.org/10.1182/blood.v92.6.2133.418k19_2133_2140.

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The small GTPase Rap1 is highly expressed in human neutrophils, but its function is largely unknown. Using the Rap1-binding domain of RalGDS (RalGDS-RBD) as an activation-specific probe for Rap1, we have investigated the regulation of Rap1 activity in primary human neutrophils. We found that a variety of stimuli involved in neutrophil activation, including fMet-Leu-Phe (fMLP), platelet-activating factor (PAF), granulocyte-macrophage colony-stimulating factor (GM-CSF), and IgG-coated particles, induce a rapid and transient Rap1 activation. In addition, we found that Rap1 is normally activated in neutrophils from chronic granulomatous disease patients that lack cytochrome b558 or p47phox and have a defective NADPH oxidase system. From these results we conclude that in neutrophils Rap1 is activated independently of respiratory burst induction. Finally, we found that Rap1 is activated by both the Ca2+ ionophore ionomycin and the phorbol ester 12-O-tetradecanoylphorbol 13-acetate (TPA), indicating that phospholipase C (PLC) activation leading to elevated levels of intracellular free Ca2+ and diacylglycerol (DAG) can mediate Rap1 activation. However, inhibition of PLC and Ca2+ depletion only marginally affected fMLP-induced Rap1 activation, suggesting that additional pathways may control Rap1 activation. © 1998 by The American Society of Hematology.

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27

Rifki, Oktay F., Brian O. Bodemann, Pavan K. Battiprolu, Michael A. White, and Joseph A. Hill. "RalGDS-dependent cardiomyocyte autophagy is required for load-induced ventricular hypertrophy." Journal of Molecular and Cellular Cardiology 59 (June 2013): 128–38. http://dx.doi.org/10.1016/j.yjmcc.2013.02.015.

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28

Peng, Wei, Jiwei Xu, Xiaotao Guan, Yao Sun, Xuejun C. Zhang, Xuemei Li, and Zihe Rao. "Structural study of the Cdc25 domain from Ral-specific guanine-nucleotide exchange factor RalGPS1a." Protein & Cell 2, no. 4 (April 2011): 308–19. http://dx.doi.org/10.1007/s13238-011-1036-z.

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29

Matsubara, Kenji, Shosei Kishida, Yoshiharu Matsuura, Hitoshi Kitayama, Makoto Noda, and Akira Kikuchi. "Plasma membrane recruitment of RalGDS is critical for Ras-dependent Ral activation." Oncogene 18, no. 6 (February 1999): 1303–12. http://dx.doi.org/10.1038/sj.onc.1202425.

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30

Sood, Raman, Izabela Makalowska, John D. Carpten, Christiane M. Robbins, Dietrich A. Stephan, Timothy D. Connors, Sharon D. Morgenbesser, et al. "The human RGL (RalGDS-like) gene: cloning, expression analysis and genomic organization." Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression 1491, no. 1-3 (April 2000): 285–88. http://dx.doi.org/10.1016/s0167-4781(00)00031-2.

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31

González-García, Ana, Catrin A. Pritchard, Hugh F. Paterson, Georgia Mavria, Gordon Stamp, and Christopher J. Marshall. "RalGDS is required for tumor formation in a model of skin carcinogenesis." Cancer Cell 7, no. 3 (March 2005): 219–26. http://dx.doi.org/10.1016/j.ccr.2005.01.029.

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32

Ferro, Elisa, and Lorenza Trabalzini. "RalGDS family members couple Ras to Ral signalling and that's not all." Cellular Signalling 22, no. 12 (December 2010): 1804–10. http://dx.doi.org/10.1016/j.cellsig.2010.05.010.

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33

O'gara, Mary Jeanne, Xian-feng Zhang, Leroy Baker, and Mark S. Marshall. "Characterization of the Ras Binding Domain of the RalGDS-Related Protein, RLF." Biochemical and Biophysical Research Communications 238, no. 2 (September 1997): 425–29. http://dx.doi.org/10.1006/bbrc.1997.7299.

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34

Li, Yajuan, Ling Wang, Jinchun Zhou, Jessica Mayeux, Yun Lian, Chandra Mohan, and Quanzhen Li. "Identification of novel autoantibodies in systemic autoimmunity using 10,000-antigen proteome arrays (P4006)." Journal of Immunology 190, no. 1_Supplement (May 1, 2013): 42.4. http://dx.doi.org/10.4049/jimmunol.190.supp.42.4.

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Abstract Systemic erythematosus lupus (SLE) is an autoimmune disease characterized by presence of autoantibodies against a broad spectrum of self-antigens. In order to identify novel serum autoantibodies associated with SLE, we utilized a protoarray bearing 10,000 antigens to screen IgG and IgM autoAbs in sera of SLE patients. 446 IgG and 1218 IgM autoAbs were significantly increased in SLE compared with health controls (p<0.05), in which 367 autAbs overlapped in IgG and IgM. Except the autoAbs previously identified in SLE patients, such as anti-DNA, Ro, La, etc., the protoarray also uncovered a group of novel autoAbs against a broad range of antigens. The increased expression of 16 novel autoantibodies in SLE, including IgG autoantibodies against APEX1, AURKA, BAG3, CSNK1G1, EIF2C1, HMGB1, IFIT5, MAPKAPK3, PADI4, PKRKA, RALGPS1, RGS3, SRP19, STIP1, UBE2S and VRK1 were further confirmed by ELISA. Gene expression analysis revealed that some of the self-antigens also significantly upregulated on transcription level. In addition to uncovering ~500 novel autoantibody specificities, the novel arrays also shed light on some of the pathogenic pathways leading to disease in systemic lupus. In conclusion, protoarray provide a powerful tool for identification of novel autoantibodies in system autoimmune diseases.

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Linnemann, Thomas, Christina Kiel, Peter Herter, and Christian Herrmann. "The Activation of RalGDS Can Be Achieved Independently of Its Ras Binding Domain." Journal of Biological Chemistry 277, no. 10 (December 17, 2001): 7831–37. http://dx.doi.org/10.1074/jbc.m110800200.

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36

Wong, Richard, and Larry A. Feig. "Tyrosine phosphorylation of RalGDS by c-Met receptor blocks its interaction with Ras." Biochemical and Biophysical Research Communications 480, no. 3 (November 2016): 468–73. http://dx.doi.org/10.1016/j.bbrc.2016.10.074.

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37

Li, Quanzhen, Jinchun Zhou, Tianfu Wu, and Chandra Mohan. "Protoarray analysis reveals novel autoantigens targeted by autoantibodies associated with DNA-repair pathway in systemic erythematosus lupus (HUM2P.330)." Journal of Immunology 192, no. 1_Supplement (May 1, 2014): 53.3. http://dx.doi.org/10.4049/jimmunol.192.supp.53.3.

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Abstract Systemic erythematosus lupus (SLE) is an autoimmune disease characterized by presence of autoantibodies (autoAbs) against a broad spectrum of self-antigens. In order to identify novel autoAbs associated with SLE, we utilized a Protoarray bearing 9,500 antigens to screen IgG and IgM autoAbs in sera of SLE patients. 446 IgG and 1218 IgM autoAbs were identified to be significantly elevated in SLE patients compared with healthy controls (p<0.05). Protoarray revealed not only the previously described autoAbs such as antibodies against dsDNA, SSA/SSB, Histone and Sm/RNP, but also uncovered autoAbs against a broad range of novel antigens including 151 nuclear-associated antigens and 150 cytoplasma or membrane-associated antigens. The Protoarray results were further validated by ELISA in a larger cohort of SLE patients and controls. Besides, 65 of the IgG autoAb-targeted proteins were also disregulated in SLE on mRNA level by microarray analysis. Pathway analysis recognized significant enrichment of antigens involved in cell proliferation and DNA repair pathways which were targeted by IgG autoAbs including APEX1, AURKA, CSNK1G1, EIF2C1, HMGB1, IFIT5, MAPKAPK3, PADI4, PRKRA, RALGPS1, UBE2S and VRK1. The elevated IgG autoAbs to APEX1 and other proteins in the pathway may reflect the compromised DNA-repair activity during DNA replication in SLE. In conclusion, identification of novel autoAbs by protoarray may shed light on some of the pathogenic pathways leading to disease in SLE.

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38

Missero, Caterina, Maria Teresa Pirro, and Roberto Di Lauro. "Multiple Ras Downstream Pathways Mediate Functional Repression of the Homeobox Gene Product TTF-1." Molecular and Cellular Biology 20, no. 8 (April 15, 2000): 2783–93. http://dx.doi.org/10.1128/mcb.20.8.2783-2793.2000.

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ABSTRACT Expression of oncogenic Ras in thyroid cells results in loss of expression of several thyroid-specific genes and inactivation of TTF-1, a homeodomain-containing transcription factor required for normal development of the thyroid gland. In an effort to understand how signal transduction pathways downstream of Ras may be involved in suppression of the differentiated phenotype, we have tested mutants of the Ras effector region for their ability to affect TTF-1 transcriptional activity in a transient-transfection assay. We find that V12S35 Ras, a mutant known to interact specifically with Raf but not with RalGDS or phosphatidylinositol 3-kinase (PI3 kinase) inhibits TTF-1 activity. Expression of an activated form of Raf (Raf-BXB) also inhibits TTF-1 function to a similar extent, while the MEK inhibitors U0126 and PD98059 partially relieve Ras-mediated inactivation of TTF-1, suggesting that the extracellular signal-regulated kinase (ERK) pathway is involved in this process. Indeed, ERK directly phosphorylates TTF-1 at three serine residues, and concomitant mutation of these serines to alanines completely abolishes ERK-mediated phosphorylation both in vitro and in vivo. Since activation of the Raf/MEK/ERK pathway accounts for only part of the activity elicited by oncogenic Ras on TTF-1, other downstream pathways are likely to be involved in this process. We find that activation of PI3 kinase, Rho, Rac, and RalGDS has no effect on TTF-1 transcriptional activity. However, a poorly characterized Ras mutant, V12N38 Ras, can partially repress TTF-1 transcriptional activity through an ERK-independent pathway. Importantly, concomitant expression of constitutive activated Raf and V12N38 Ras results in almost complete loss of TTF-1 activity. Our data indicate that the Raf/MEK/ERK cascade may act in concert with an as-yet-uncharacterized signaling pathway activated by V12N38 Ras to repress TTF-1 function and ultimately to inhibit thyroid cell differentiation.

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39

Mazhab-Jafari, Mohammad T., Christopher B. Marshall, Matthew J. Smith, Geneviève M. C. Gasmi-Seabrook, Peter B. Stathopulos, Fuyuhiko Inagaki, Lewis E. Kay, Benjamin G. Neel, and Mitsuhiko Ikura. "Oncogenic and RASopathy-associated K-RAS mutations relieve membrane-dependent occlusion of the effector-binding site." Proceedings of the National Academy of Sciences 112, no. 21 (May 4, 2015): 6625–30. http://dx.doi.org/10.1073/pnas.1419895112.

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K-RAS4B (Kirsten rat sarcoma viral oncogene homolog 4B) is a prenylated, membrane-associated GTPase protein that is a critical switch for the propagation of growth factor signaling pathways to diverse effector proteins, including rapidly accelerated fibrosarcoma (RAF) kinases and RAS-related protein guanine nucleotide dissociation stimulator (RALGDS) proteins. Gain-of-function KRAS mutations occur frequently in human cancers and predict poor clinical outcome, whereas germ-line mutations are associated with developmental syndromes. However, it is not known how these mutations affect K-RAS association with biological membranes or whether this impacts signal transduction. Here, we used solution NMR studies of K-RAS4B tethered to nanodiscs to investigate lipid bilayer-anchored K-RAS4B and its interactions with effector protein RAS-binding domains (RBDs). Unexpectedly, we found that the effector-binding region of activated K-RAS4B is occluded by interaction with the membrane in one of the NMR-observable, and thus highly populated, conformational states. Binding of the RAF isoform ARAF and RALGDS RBDs induced marked reorientation of K-RAS4B from the occluded state to RBD-specific effector-bound states. Importantly, we found that two Noonan syndrome-associated mutations, K5N and D153V, which do not affect the GTPase cycle, relieve the occluded orientation by directly altering the electrostatics of two membrane interaction surfaces. Similarly, the most frequent KRAS oncogenic mutation G12D also drives K-RAS4B toward an exposed configuration. Further, the D153V and G12D mutations increase the rate of association of ARAF-RBD with lipid bilayer-tethered K-RAS4B. We revealed a mechanism of K-RAS4B autoinhibition by membrane sequestration of its effector-binding site, which can be disrupted by disease-associated mutations. Stabilizing the autoinhibitory interactions between K-RAS4B and the membrane could be an attractive target for anticancer drug discovery.

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40

HUMPHREY, D., J. KWIATKOWSKA, E. P. HENSKE, J. L. HAINES, D. HALLEY, M. SLEGTENHORST, and D. J. KWIATKOWSKI. "Cloning and evaluation of RALGDS as a candidate for the tuberous sclerosis gene TSC1." Annals of Human Genetics 61, no. 4 (July 1997): 299–305. http://dx.doi.org/10.1046/j.1469-1809.1997.6140299.x.

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41

HUMPHREY, D., J. KWIATKOWSKA, E. P. HENSKE, J. L. HAINES, D. HALLEY, M. van SLEGTENHORST, and D. J. KWIATKOWSKI. "Cloning and evaluation of RALGDS as a candidate for the tuberous sclerosis gene TSC1." Annals of Human Genetics 61, no. 4 (July 1997): 299–305. http://dx.doi.org/10.1017/s0003480097006246.

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42

Murphy, Gretchen A., Suzanne M. Graham, Staeci Morita, Sarah E. Reks, Kelley Rogers-Graham, Anne Vojtek, Grant G. Kelley, and Channing J. Der. "Involvement of Phosphatidylinositol 3-Kinase, but Not RalGDS, in TC21/R-Ras2-mediated Transformation." Journal of Biological Chemistry 277, no. 12 (January 11, 2002): 9966–75. http://dx.doi.org/10.1074/jbc.m109059200.

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43

Liu, Shan, Congyu Shi, Xiaoyi Wang, Xiangrui Ma, and Pan Gao. "Low expression of RalGAPs associates with the poorer overall survival of head and neck squamous cell carcinoma." Translational Cancer Research 10, no. 12 (December 2021): 5085–94. http://dx.doi.org/10.21037/tcr-21-1489.

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44

Kikuchi, Akira, and Lewis T. Williams. "Regulation of Interaction ofrasp21 with RalGDS and Raf-1 by Cyclic AMP-dependent Protein Kinase." Journal of Biological Chemistry 271, no. 1 (January 5, 1996): 588–94. http://dx.doi.org/10.1074/jbc.271.1.588.

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45

Isomura, M., K. Okui, T. Fujiwara, S. Shin, and Y. Nakamura. "Isolation and mapping of RAB2L, a human cDNA that encodes a protein homologous to RalGDS." Cytogenetic and Genome Research 74, no. 4 (1996): 263–65. http://dx.doi.org/10.1159/000134431.

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46

Peterson, Scott N., Lorenza Trabalzini, Teresa R. Brtva, Thomas Fischer, Daniel L. Altschuler, Paola Martelli, Eduardo G. Lapetina, Channing J. Der, and Gilbert C. White. "Identification of a Novel RalGDS-related Protein as a Candidate Effector for Ras and Rap1." Journal of Biological Chemistry 271, no. 47 (November 22, 1996): 29903–8. http://dx.doi.org/10.1074/jbc.271.47.29903.

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47

Inoue, Kyoko, Till Maurer, Hiroaki Yamada, Christian Herrmann, Gudrun Horn, Hans Robert Kalbitzer, and Kazuyuki Akasaka. "High-pressure NMR study of the complex of a GTPase Rap1A with its effector RalGDS." FEBS Letters 506, no. 3 (September 12, 2001): 180–84. http://dx.doi.org/10.1016/s0014-5793(01)02809-5.

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48

Senga, Takeshi, Takashi Iwamoto, Toshio Kitamura, Yozo Miyake, and Michinari Hamaguchi. "JAK/STAT3-dependent Activation of the RalGDS/Ral Pathway in M1 Mouse Myeloid Leukemia Cells." Journal of Biological Chemistry 276, no. 35 (June 29, 2001): 32678–81. http://dx.doi.org/10.1074/jbc.m105749200.

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49

Yoshizawa, Ryo, Nobuhisa Umeki, Masataka Yanagawa, Masayuki Murata, and Yasushi Sako. "Single-molecule fluorescence imaging of RalGDS on cell surfaces during signal transduction from Ras to Ral." Biophysics and Physicobiology 14 (2017): 75–84. http://dx.doi.org/10.2142/biophysico.14.0_75.

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Masuhara, Kaori, Seigo Iwata, Nobuhisa Umeki, and Shinsaku Maruta. "Photo-Regulation of the Interaction between Ras and Ralgds using GTP Analogues Composed of Photochromic Molecules." Biophysical Journal 108, no. 2 (January 2015): 614a. http://dx.doi.org/10.1016/j.bpj.2014.11.3340.

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