• The normal rate of Ras catalytic GTPase (GTP hydrolysis) activity can be increased by proteins of the RasGAP family, which bind to Ras and increase its catalytic rate by a factor of one thousand - in effect, increasing the rate at which Ras is inactivated. (bionity.com)
  • Guanine nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs) accelerate GTP loading and hydrolysis, respectively. (nih.gov)
  • These accessory proteins play a fundamental role in regulating activities of RAS superfamily small GTPase via a conserved guanine binding (G)-domain, which consists of five G motifs. (nih.gov)
  • We have revealed the design principles and functions of "pH sensors" described as endogenous proteins regulated within the cellular pH range, including guanine nucleotide exchange factors regulating cell polarity (Frantz et al. (ucsf.edu)
  • Like all members of the Ras superfamily, the Rho proteins cycle between active GTP-bound and inactive GDP-bound conformational states. (embl-heidelberg.de)
  • Activation of Rho proteins through release of bound GDP and subsequent binding of GTP, is catalysed by guanine nucleotide exchange factors (GEFs) in the Dbl family. (embl-heidelberg.de)
  • It does not share significant sequence homology with other subtypes of small G-protein GEF motifs such as the Cdc25 domain and the Sec7 domain, which specifically interact with Ras and ARF family small GTPases, respectively, nor with other Rho protein interactive motifs, indicating that the Dbl family proteins are evolutionarily unique. (embl-heidelberg.de)
  • The guanine nucleotide exchange factor (GEF) Dbl targets Rho family proteins thereby stimulating their GDP/GTP exchange, and thus is believed to be involved in receptor-mediated regulation of the proteins. (embl-heidelberg.de)
  • The encoded protein belongs to a family of cytoplasmic proteins that activate the Ras-like family of Rho proteins by exchanging bound GDP for GTP. (antibodies-online.com)
  • In addition, cAMP binds to and regulates the function of ion channels such as the HCN channels and a few other cyclic nucleotide-binding proteins such as Epac1 and RAPGEF2 . (wikipedia.org)
  • In 1998 a family of cAMP-sensitive proteins with guanine nucleotide exchange factor (GEF) activity was discovered. (wikipedia.org)
  • These are termed Exchange proteins activated by cAMP (Epac) and the family comprises Epac1 and Epac2 . (wikipedia.org)
  • A novel membrane factor stimulates guanine nucleotide exchange reaction of ras proteins. (wikidata.org)
  • Guanine nucleotide exchange factors ("GEFs") stimulate the dissociation of the GTP hydrolytic product, GDP, from small GTP-binding proteins, to promote the binding of a new GTP molecule. (justia.com)
  • When GTP is bound, for instance, Ras proteins can interact with effectors and other molecules to affect cell proliferation, differentiation and apoptosis. (justia.com)
  • We have previously reported that the posttranslational processing of Ki-ras p21 is essential for its interaction with one of its GDP/GTP exchange proteins named smg GDS. (fujita-hu.ac.jp)
  • We show that the posttranslationally fully processed Ki- and Ha-ras p21s activate yeast adenylate cyclase far more effectively than do the unprocessed proteins. (fujita-hu.ac.jp)
  • Rho (A, B, & C) proteins are members of the Ras superfamily of GTPases. (phosphosolutions.com)
  • Interconversion between these forms is controlled by guanine nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs). (phosphosolutions.com)
  • Rab proteins constitute the largest family of Ras-related small G proteins and play a role in regulating the specificity of membrane trafficking (63, 78). (pancreapedia.org)
  • Similar to other small G proteins, the guanine binding state of Rab3 proteins is regulated by guanine nucleotide exchange proteins or factors (GEPs or GEFs) and GTPase activating proteins (GAPs). (pancreapedia.org)
  • Like other members of the RAS superfamily, ARF family proteins can be activated by guanine-nucleotide exchange factors (GEFs) and inactivated by GTPase-activating proteins (GAPs) [ 9 ]. (biomedcentral.com)
  • Programmable DNA binding proteins have emerged as an exciting platform for engineering synthetic transcription factors for modulating endogenous gene expression 5 - 11 . (cdc.gov)
  • Thus, upon binding to GTP, the duration of Ras-GTPase activity is limited by the rate at which it hydrolyzes its bound GTP to GDP. (bionity.com)
  • Once released from SOS, the Ras-GTPase quickly binds fresh guanine nucleotide from the cytosol. (bionity.com)
  • This may be explained because the SOS1 protein adopts an auto-inhibited conformation dependent on multiple domain-to-domain interactions that cooperate to block access of the SOS1 catalytic core to its Ras-GTPase targets [7] . (bionity.com)
  • Ras is a GTPase that is anchored to the intracellular side of the plasma membrane through its post-translational lipid modifications. (biolegend.com)
  • RAPGEF1 is a guanine nucleotide exchange factor responsible for transmitting extracellular signals to the Ras family of GTPase located at the inside of membrane. (authorea.com)
  • GEFs regulate the activity of members of the Ras superfamily of GTPases. (medscape.com)
  • They play an important role in the recognition of regulatory factors (GEFs and GAPs) and effectors. (nih.gov)
  • As a proangiogenic response effecter, the interaction of Sema4D with plexin-B1 is dependent on the COOH-terminal PDZ-binding motif of plexin-B1, which binds two guanine nucleotide exchange factors (GEFs) for Rho and is mediated by the activation of Rho-initiated (Ras homolog gene family) pathways ( 4 - 8 ). (jcancer.org)
  • TARP functions by binding two distinct Rac guanine nucleotide exchange factors (GEFs), Sos1 and Vav2, in a phosphotyrosine-dependent manner. (elsevierpure.com)
  • Its function is to release guanosine diphosphate, GDP, from the signaling protein RAS, thus increasing the activity of RAS by allowing it to bind to guanosine triphosphate, GTP, returning it to its active state. (wikipedia.org)
  • Ras-GRF1 mediates the activation of RAS via Ca2+ bound calmodulin protein. (wikipedia.org)
  • Ras-GRF1 is a paternally expressed imprinted gene, meaning that only the paternal allele of the gene is translated into protein. (wikipedia.org)
  • Ras-GTPases act as molecular switches that bind to downstream effectors, such as the protein kinase c-Raf , and localizes them to the membrane resulting in their activation. (bionity.com)
  • This causes adaptor protein GRB2 to recruit SOS, a guanine nucleotide exchange factor, which then facilitates binding of GTP to Ras. (biolegend.com)
  • GTP-bound Ras activates Raf to trigger a phosphorylation cascade involving mitogen-activated protein kinases (MEKs). (biolegend.com)
  • Antigen binding to the T cell receptor (TCR) can also lead to Ras signaling through activation of phospholipase C (PLC) and protein kinase C (PKC). (biolegend.com)
  • Metformin Enhances the Effect of Regorafenib and Inhibits Recurrence and Metastasis of Hepatic Carcinoma After Liver Resection via Regulating Expression of Hypoxia Inducible Factors 2α (HIF-2α) and 30 kDa HIV Tat-Interacting Protein (TIP30). (cancerindex.org)
  • Disclaimer note: The observed molecular weight of the protein may vary from the listed predicted molecular weight due to post translational modifications, post translation cleavages, relative charges, and other experimental factors. (novusbio.com)
  • Ras effector protein, which may serve as an inhibitory modulator of neuronal plasticity in aversive memory formation. (novusbio.com)
  • First, by competing with RAF1 protein for binding to activated Ras. (novusbio.com)
  • Although one effector of Epac is the Ras-related G protein Rap1, it is not fully understood what the functional consequences of Epac-mediated signal transduction are at the cellular level. (nih.gov)
  • The LIN-14 transcription factor likely directly represses dma-1 gene expression through a transcriptional means, whereas the LIN-41 tripartite motif protein likely indirectly promotes dma-1 gene expression through a posttranscriptional means. (stanford.edu)
  • The shelf life is related to many factors, storage state, buffer ingredients, storage temperature and the stability of the protein itself. (cusabio.com)
  • In doing so, this GEF-facilitated exchange of GDP for GTP is associated with structural changes in the GTP-binding protein which influence the degree to which the GTP-binding protein can interact with other molecules. (justia.com)
  • Mammalian ras genes substitute for the yeast RAS gene, and their products activate adenylate cyclase in yeast cells, although the direct target protein of mammalian ras p21s remains to be identified. (fujita-hu.ac.jp)
  • The previous and present results suggest that the posttranslational processing of ras p21s is important for their interaction not only with smg GDS but also with the target protein. (fujita-hu.ac.jp)
  • Grb2 or growth factor receptor-bound protein 2 is an adaptor protein involved in the Ras signaling pathway. (uvm.edu)
  • In cell signalling , Son of Sevenless , or SOS , is a gene encoding a guanine nucleotide exchange factor that acts on Ras - GTPases . (bionity.com)
  • Ras-GTPases are considered inactive when bound to guanosine diphosphate (GDP) and active when bond to guanosine triphosphate (GTP). (bionity.com)
  • As the name implies, Ras-GTPases possess intrinsic enzymatic activity that converts GTP to GDP plus phosphate. (bionity.com)
  • SOS (and other guanine nucleotide exchange factors) act by binding Ras-GTPases and forcing them to release of their bound nucleotide (usually GDP). (bionity.com)
  • Biochemically, these mutations have been shown to similarly effect aberrant activation of the catalytic domain towards Ras-GTPases. (bionity.com)
  • RAS is a founding member of the RAS superfamily of GTPases. (nih.gov)
  • Guanine nucleotide dissociation stimulators (GDSs, or exchange factors), such as RALGDS, are effectors of Ras-related GTPases (see MIM 190020) that participate in signaling for a variety of cellular processes. (cancerindex.org)
  • Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases Also called Dbl-homologous (DH) domain. (embl-heidelberg.de)
  • These include four regions participating in guanine nucleotide binding, and effector region corresponding to the effector region in Ras, and a CXC prenylation motif at the C-terminal (45). (pancreapedia.org)
  • Post-translational modification within the G4 and G5 motifs activates RAS by populating the GTP-bound "ON" state, either through enhancement of intrinsic guanine nucleotide exchange or impairing GAP-mediated down-regulation. (nih.gov)
  • In its active form, GTP-bound RAS is responsible for numerous critical cellular processes. (rcsb.org)
  • Promotes the exchange of Ras-bound GDP by GTP. (cusabio.com)
  • one binds to phosphorylated tyrosines (the upstream molecule) and the other binds to a proline rich motif, predominately on the guanine nucleotide exchange factor SOS (the downstream molecule) (2). (uvm.edu)
  • Son of sevenless homologue 1 (SOS1) is a guanine nucleotide exchange factor that catalyzes the exchange of GDP for GTP on RAS. (rcsb.org)
  • Using structure-guided design, we discovered small molecules that increase nucleotide exchange on RAS in vitro at submicromolar concentrations, bind to SOS1 with low double-digit nanomolar affinity, rapidly enhance cellular RAS-GTP levels, and invoke biphasic signaling changes in phosphorylation of ERK 1/2. (rcsb.org)
  • This ultimately results in the translocation of ERK to the nucleus where it phosphorylates and activates a number of transcription factors like Elk1, initiating expression of genes that promote cell survival and growth. (biolegend.com)
  • RAS is activated by GTP loading and deactivated upon GTP hydrolysis to GDP. (nih.gov)
  • Alongside its regulation of learning and memory, Ras-GRF1 has exhibited the ability to impact pancreatic β-cell proliferation. (wikipedia.org)
  • These motifs are responsible for the recognition of the guanine moiety in GTP and GDP, and contain residues that undergo post-translational modifications that underlie new mechanisms of RAS regulation. (nih.gov)
  • A common feature of these genes is that their products have all been strongly implicated as positive regulators of the Ras/ MAP kinase signal transduction pathway. (bionity.com)
  • Ras activated by this mechanism drives the PI3K pathway to initiate expression of cell growth genes. (biolegend.com)
  • Upon stimulation by growth factors, cytokines, neurotransmitters, or other signals, receptor tyrosine kinases on the cell surface will be autophosphorylated. (biolegend.com)
  • A Ras-GRF1/ERK pathway has also been found to affect the activity of LTP in medium spiny neuron (MSN) pathways. (wikipedia.org)
  • Ras-GRF1 knockout mice treated with HFS-LTP have exhibited the inability to induce LTP in direct MSN pathways. (wikipedia.org)
  • It has been hypothesized that inactivation of the RASSF1A tumor suppressor facilitates K-RAS-mediated transformation by uncoupling it from apoptotic pathways such as the Hippo pathway. (cancerindex.org)
  • Since GTP is roughly ten times more abundant than GDP in the cytosol, this usually results in Ras activation. (bionity.com)
  • Ras-GRF1 has also been shown to be upstream from IGF1, allowing it to control growth in mice. (wikipedia.org)
  • The mammalian homologue similarly functions downstream of many growth factor and adhesion receptors. (bionity.com)
  • The present invention relates to diagnosing abnormal cell proliferation in biological samples and screening for drugs which inhibit, reduce or abolish cell growth, especially tumorigenic cell growth, by detecting a phosphovariant isoform of a guanine nucleotide exchange factor biomarker, such as the novel GEF-H1S. (justia.com)
  • SOS-1 is a guanine nucleotide-exchange factor that functions in the transduction of signals that control cell growth and differentiation 9,10 . (bvsalud.org)
  • Mutant K-RAS has been shown to have both tumor-promoting and -suppressing functions, and growing evidence suggests that the RASSF family of tumor suppressors can act as RAS apoptosis and senescence effectors. (cancerindex.org)
  • Reduction of β-cell mass and area has correlated to a decrease in circulating insulin levels, exposing a Ras-GRF1 signaling pathway that regulates glucose metabolism. (wikipedia.org)
  • Ras-GRF1 knockout mice have expressed decreased pancreatic β-cell concentration and activity. (wikipedia.org)
  • In this way, Ras-GRF1 has a key role in regulating the RAS signaling pathway. (wikipedia.org)
  • Here, we provide a comprehensive review of post-translational modifications in the RAS G4 and G5 motifs, and describe the role of these modifications in RAS activation as well as potential applications for cancer therapy. (nih.gov)
  • Semaphorin 4D (Sema4D) has been proven to be one of the hypoxia effectors regulated by hypoxia inducible factor (HIF-1) in multiple cells, and play a role in angiogenesis like VEGF. (jcancer.org)
  • Additionally, BTA-EG 4 requires APP to regulate dendritic spine density through a Ras signaling-dependent mechanism. (jneurosci.org)
  • There are three biomarkers of effect currently being applied to measure PO exposure in humans: DNA adducts, hemoglobin adducts, and sister chromatid exchanges (SCE). (who.int)
  • Loss-of-function mutations in the lin-4 microRNA gene cause limited dendritic outgrowth, whereas loss-of-function mutations in its direct target, the lin-14 transcription factor gene, cause precocious and excessive outgrowth. (stanford.edu)
  • Approach for targeting Ras with small molecules that activate SOS-mediated nucleotide exchange. (rcsb.org)
  • In human lung tumors, combined activation of K-RAS and inactivation of RASSF1A is closely associated with the development of the most aggressive and worst prognosis tumors. (cancerindex.org)
  • Here, we describe the first transgenic mouse model for activation of K-RAS in the lung in a RASSF1A-defective background. (cancerindex.org)
  • Ras-GRF1 knockout mice have been shown to have learning and memory deficits associated with dysregulation of this pathway. (wikipedia.org)
  • Ras-GRF1 knockout mice, induced with high frequency stimulation to induce LTP (HFS-LTP), displayed the inability to retain memory and distinguish similar concepts. (wikipedia.org)
  • To understand the structural basis for this effect we compared the structure of autoinhibited RasGRP1, determined previously, to those of active RasGRP4:H-Ras and RasGRP2:Rap1b complexes. (rcsb.org)
  • The structure of the Rabs changes upon binding GTP and mutant Rab3 species have been described similar to Ras that are locked into active and inactive configurations (6). (pancreapedia.org)
  • In this investigation, we have studied whether the posttranslational processing of Ki- and Ha-ras p21s is critical for their stimulation of yeast adenylate cyclase in a cell-free system. (fujita-hu.ac.jp)
  • Age and the high mRNA expression of ARL9 were independent risk factors for a poor prognosis in patients with colon adenocarcinoma. (biomedcentral.com)