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GTP-Binding ProteinsGuanosine TriphosphateGuanineGTP PhosphohydrolasesMolecular Sequence DataGuanosine DiphosphateGuanine Nucleotide Exchange FactorsAmino Acid SequenceGuanosine 5'-O-(3-Thiotriphosphate)Guanine NucleotidesMonomeric GTP-Binding Proteinsrab GTP-Binding ProteinsProtein BindingADP-Ribosylation FactorsPertussis ToxinBase SequenceVirulence Factors, BordetellaThionucleotidesPhosphatidylinositol 3-KinasesSequence Homology, Amino AcidGTPase-Activating ProteinsAdenosine Diphosphate RiboseSignal TransductionProtein-Serine-Threonine Kinasesrho GTP-Binding ProteinsKineticsMutationCloning, MolecularADP Ribose TransferasesBotulinum ToxinsMAP Kinase Signaling SystemProtein KinasesrhoA GTP-Binding Proteinras ProteinsCell MembraneCalcium-Calmodulin-Dependent Protein KinasesCarrier ProteinsBinding SitesProtein Kinase InhibitorsCattleSaccharomyces cerevisiaePoly(A)-Binding Proteinssrc-Family KinasesProtein Kinase CProtein Structure, TertiaryCyclic AMP-Dependent Protein KinasesPhosphorylationCell LineRecombinant Proteinsp38 Mitogen-Activated Protein KinasesGuanylyl ImidodiphosphateMitogen-Activated Protein Kinase 1DNA-Binding Proteinsp21-Activated KinasesTransfectionEnzyme ActivationGTP CyclohydrolaseGuanine DeaminaseRecombinant Fusion ProteinsJNK Mitogen-Activated Protein KinasesMitogen-Activated Protein Kinase KinasesRNA, MessengerMitogen-Activated Protein Kinase 3Protein-Tyrosine KinasesModels, MolecularBlotting, WesternMAP Kinase Kinase KinasesEscherichia coliHydrolysisDNAGuanosine MonophosphateTacrolimus Binding ProteinsCreatine KinaseCDC2 Protein KinaseCells, CulturedCyclin-Dependent KinasesPhosphoproteinsCalciumCasein Kinase IISubstrate SpecificityMutagenesis, Site-DirectedeIF-2 KinaseNuclear Proteins3T3 CellsCasein KinasesProto-Oncogene Proteins p21(ras)Ribosomal Protein S6 KinasesMembrane ProteinsHeLa CellsProteinsPyruvate KinaseSequence AlignmentPoly(A)-Binding Protein IProto-Oncogene ProteinsThymidine KinaseElectrophoresis, Polyacrylamide GelMolecular WeightTranscription FactorsAdenosine TriphosphateMitogen-Activated Protein Kinases
Nucleotide ExchanPathwaysMAPKPhosphatidylinositolTyrosine kinaseEffectorGEFsGuanosine triphosphataseHydrolysisGTPaseSubfamilyAmyloidActivationMutationsDifferentiationAssaysExtracellular matrixRegulateReceptorInteractionsMovementGenesExchangeReceptorsSymbolInactiveMutantsDownstreamLipidCellular processesFactorsDependentMembraneTumorSmallGeneInhibitionSpectrinFoundActiveLevelsFactorCellsDomainsSourceMajorMultipleAlphaHighly
Nucleotide Exchan1
  • This study reveals a noncanonical role of AMP-activated kinase in which the α subunit C-terminal regulatory domain serves as a guanine-nucleotide-exchange factor for Arf6 during glucose deprivation. (biologists.com)
Pathways12
  • These guanosine triphosphatases bind GTP causing the activation of mitogen activated protein kinase (MAPK), phosphoinositide-3-kinase (PI3K) and Ras-like (RAL) pathways [ 1 ]. (biomedcentral.com)
  • What pathways are this gene/protein implicaed in? (cancerindex.org)
  • Ras proteins are membrane-bound small GTPases that act as molecular transducers, coupling cell surface receptors to intracellular effector pathways to regulate cellular processes such as cell proliferation, differentiation, migration, and apoptosis [ 3 ] [ 4 ] . (encyclopedia.pub)
  • Within neurons, multiple pathways are known to transport proteins and transmitters to the cell surface. (sdbonline.org)
  • Another distinction that has been drawn contrasts the constitutive and the regulated pathways to distinguish the ongoing transport of protein and lipid to the cell surface from the ability to secrete hormones and transmitters in response to specific stimuli. (sdbonline.org)
  • Two important pathways were examined in the current study: (1) a basic pathway of exocytosis that brings new proteins to the cell surface and permits the cell to grow, and (2) synaptic transmission, a specialized form of exocytosis, regulated by Ca 2+ entry, in which vesicles already present at synapses fuse with the membrane and recycle locally (Murthy, 2003). (sdbonline.org)
  • Through these interactions, PH domains play a role in recruiting proteins to different membranes, thus targeting them to appropriate cellular compartments or enabling them to interact with other components of the signal transduction pathways. (embl.de)
  • R-Ras proteins function distinctly from classic Ras proteins by regulating distinct signaling pathways that promote MPNST tumorigenesis by mediating migration and invasion. (biomedcentral.com)
  • We have previously shown that three related Ras proteins (the classic Ras proteins) are highly activated in malignant peripheral nerve sheath tumor (MPNST) cells with neurofibromin loss and that they drive cancer cell proliferation and survival by activating multiple cellular signaling pathways. (biomedcentral.com)
  • We examined the activation of cytoplasmic signaling pathways in the presence and absence of R-Ras signaling and found that R-Ras proteins regulated 13 signaling pathways distinct from those regulated by classic Ras proteins. (biomedcentral.com)
  • Patrick A. Lewis ABSTRACT Leucine-rich repeat kinase 2 (LRRK2) is a multidomain scaffolding protein with dual guanosine triphosphatase ( GTPase ) and kinase enzymatic activities, providing this protein with the capacity to regulate a multitude of signalling pathways. (biologists.com)
  • Analysis with the RAS effector-loop mutants that interact specifically with Raf, Ral GDS pathways highlighted the importance of the RalGDS pathways in the regulation of S100A10 gene expression. (oncotarget.com)
MAPK1
  • GTP-bound LET-60 then activates the LIN-45 (Raf) 13 , MEK-2 14 and MPK-1 (MAPK) kinase cascade, which is facilitated by the scaffold protein KSR. (hideyuki-ts.com)
Phosphatidylinositol2
  • Active GTP-bound Ras interacts with several effector proteins: among the best characterized are the Raf kinases, phosphatidylinositol 3-kinase (PI3K), RalGEFs and NORE/MST1. (umbc.edu)
  • Point mutations cluster into the positively charged end of the molecule around the predicted binding site for phosphatidylinositol lipids. (embl.de)
Tyrosine kinase1
  • Mutations in Brutons tyrosine kinase (Btk) within its PH domain cause X-linked agammaglobulinaemia (XLA) in patients. (embl.de)
Effector1
  • Mouse protein citron, a putative rho/rac effector that binds to the GTP-bound forms of rho and rac. (embl.de)
GEFs2
Guanosine triphosphatase1
Hydrolysis1
  • The disease mechanism underlying these variants is dependent on the specific defect, as some reduce intrinsic GTP hydrolysis, while others result in an insensitivity to GAP-mediated GTP hydrolysis [ 2 ]. (biomedcentral.com)
GTPase4
  • Ras is a small GTPase that operates as a binary molecular switch between a GDP-bound inactive and GTP-bound active state. (rupress.org)
  • Regulators of small G-proteins like guanine nucleotide releasing factor GNRP (Ras-GRF) (which contains 2 PH domains), guanine nucleotide exchange proteins like vav, dbl, SoS and Saccharomyces cerevisiae CDC24, GTPase activating proteins like rasGAP and BEM2/IPL2, and the human break point cluster protein bcr. (embl.de)
  • Loss of the Ras GTPase-activating protein neurofibromin promotes nervous system tumor pathogenesis in patients with neurofibromatosis type 1 (NF1). (biomedcentral.com)
  • engagement triggers rapid GTP-loading of the small GTPase Rac as a master regulator of cytoskeletal rearrangements and lamellipodia-driven internalization. (biologists.com)
Subfamily3
  • Tyrosine protein kinases belonging to the Btk/Itk/Tec subfamily. (embl.de)
  • Neurofibromin loss potentially hyperactivates classic Ras (H-Ras, N-Ras, K-Ras), M-Ras, and R-Ras (R-Ras, R-Ras2/TC21) subfamily proteins. (biomedcentral.com)
  • Cells were transfected with doxycycline-inducible vectors expressing either a pan-inhibitor of the R-Ras subfamily [dominant negative (DN) R-Ras] or enhanced green fluorescent protein (eGFP). (biomedcentral.com)
Amyloid3
  • amyloid beta precursor protein binding f. (gsea-msigdb.org)
  • The tetra(ethylene glycol) derivative of benzothiazole aniline, BTA-EG 4 , is a novel amyloid-binding small molecule that can penetrate the blood-brain barrier and protect cells from Aβ-induced toxicity. (jneurosci.org)
  • We report here that BTA-EG 4 decreases Aβ levels, alters cell surface expression of amyloid precursor protein (APP), and improves memory in wild-type mice. (jneurosci.org)
Activation4
  • This G-LISA™ Rho activation assay measures the levels of GTP-loaded RhoA in cells. (cytoskeleton.com)
  • We assessed the expression and activation of these proteins in MPNST cells and inhibited them to determine the effect this had on proliferation, migration, invasion, survival and the phosphoproteome. (biomedcentral.com)
  • Mutations of the NF1 gene potentially results in the activation of multiple Ras proteins, which are key regulators of many biologic effects. (biomedcentral.com)
  • Here, we examined the expression, activation and action of R-Ras proteins in MPNST cells that have lost neurofibromin. (biomedcentral.com)
Mutations3
  • Scope includes mutations and abnormal protein expression. (cancerindex.org)
  • Additionally, Ras proteins are recognized as major oncogenes, as mutations in all three Ras genes occur in approximately 30% of human cancers [ 10 ] . (encyclopedia.pub)
  • sec5 mutations have been identified and characterized in Drosophila in order to delineate the role of the protein in neurons and particularly at synapses. (sdbonline.org)
Differentiation2
Assays1
  • Since the Rho-GTP affinity wells are supplied as strips and the strips can be broken into smaller pieces, each kit can be used for anywhere from one to multiple assays. (cytoskeleton.com)
Extracellular matrix1
  • Ras signaling is activated by cellular receptors including receptor tyrosine kinases (RTKs), G-protein coupled receptors (GPCRs), cytokines receptors, and extracellular matrix receptors [ 12 ] . (encyclopedia.pub)
Regulate1
  • Inhibition of R-Ras/R-Ras2 and ROCK1 signaling also triggered the accumulation of abnormal intracellular vesicles, indicating that these signaling molecules regulate the movement of proteins and other molecules in the cellular interior. (biomedcentral.com)
Receptor4
Interactions1
  • Members of the benzothiazole aniline (BTA) family of compounds are characterized as a class of small molecules that have shown great promise in preventing Aβ-protein interactions. (jneurosci.org)
Movement2
  • Mass spectrometry-based phosphoproteomics identified thirteen protein networks distinctly regulated by DN R-Ras, including multiple networks regulating cellular movement and morphology. (biomedcentral.com)
  • Cancer cells that have acquired an invasive phenotype release proteases that attack and digest the protein component of the matrix that would restrict the movement of these malignant cells. (oncotarget.com)
Genes2
  • In humans, three Ras genes ( H-ras , N-ras, and K-ras ) encode four distinct Ras proteins: H-Ras, N-Ras, K-Ras4A, and K-RasS4B, the latter 2 resulting from alternative RNA splicing of the K-ras gen. (encyclopedia.pub)
  • This domain occurred 125 times on human genes ( 227 proteins). (umbc.edu)
Exchange1
  • 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)
Receptors1
  • The uPA converts cell surface-bound plasminogen to plasmin, a process that is regulated by the binding of plasminogen to specific receptors on the cell surface, however, the identity of the plasminogen receptors that function in this capacity is unclear. (oncotarget.com)
Symbol1
Inactive1
  • Ras proteins act as molecular switches that cycle between two conformational states: an active GTP-bound state and an inactive GDP-bound state. (encyclopedia.pub)
Mutants1
  • The exocyst complex, a set of eight proteins first identified from secretory mutants in yeast, is an attractive candidate for mediating directed traffic. (sdbonline.org)
Downstream1
  • GTP binding to Ras induces changes in conformation, mainly in two regions named switch I and switch II, that greatly increase the affinity of Ras for its downstream effectors [ 14 ] [ 15 ] . (encyclopedia.pub)
Lipid2
  • Most Ras proteins contain a lipid modification site at the C-terminus, with a typical sequence motif CaaX, where a = an aliphatic amino acid and X = any amino acid. (umbc.edu)
  • Lipid binding is essential for membrane attachment, a key feature of most Ras proteins. (umbc.edu)
Cellular processes1
  • Ras proteins are essential mediators of a multitude of cellular processes, and its deregulation is frequently associated with cancer appearance, progression, and metastasis. (encyclopedia.pub)
Factors1
  • 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)
Dependent2
  • Notch signalling inhibits MAKP, and LET-60 in P5.p and P7.p cells uses a RAL-1 dependent pathway to commit to 2 \(^\circ\) fate. (hideyuki-ts.com)
  • cyclin dependent kinase inhibitor 1C [So. (gsea-msigdb.org)
Membrane5
  • Such a membrane-anchoring strategy has been adopted by a wide range of signaling proteins ( Fivaz and Meyer, 2003 ) with significant variations in the structure of these motifs (see Table S1). (rupress.org)
  • glycosylated integral membrane protein. (gsea-msigdb.org)
  • Such processes require membrane traffic to particular domains of the cell surface, in order to insert proteins at restricted regions of the membrane, to enlarge particular regions of the cell membrane, or to signal asymmetrically to neighboring cells. (sdbonline.org)
  • Neurons generate their polarity by directing membrane traffic to growing neurites and growth cones, and by sorting proteins differentially between the axon and dendrites. (sdbonline.org)
  • This protein is required for many aspects of membrane traffic within neurons, including the elaboration of neurites, but the release of neurotransmitter at the synapse is independent of this exocyst component (Murthy, 2003). (sdbonline.org)
Tumor1
  • We have shown that classic Ras proteins promote proliferation and survival, but not migration, in malignant peripheral nerve sheath tumor (MPNST) cells. (biomedcentral.com)
Small2
  • Metformin (MTF) has been reported to target NLK (Nemo-like kinase) to inhibit non-small lung cancer cells. (cancerindex.org)
  • Pleckstrin homology (PH) domains are small modular domains that occur in a large variety of proteins. (embl.de)
Gene3
Inhibition1
  • Closer study of an R-Ras regulated pathway containing the signaling protein ROCK1 showed that inhibition of either R-Ras, R-Ras2 or ROCK1 similarly impaired cellular migration and invasion and altered cellular morphology. (biomedcentral.com)
Spectrin1
  • Cytoskeletal proteins such as dynamin (see IPR001401 ), Caenorhabditis elegans kinesin-like protein unc-104 (see IPR001752 ), spectrin beta-chain, syntrophin (2 PH domains) and S. cerevisiae nuclear migration protein NUM1. (embl.de)
Found1
Active1
Levels1
  • In ATM knockdown cells, it was also revealed that the protein expression levels of HIF-1α and antiapoptotic BCL-2/BAD were upregulated. (bvsalud.org)
Factor1
Cells2
  • Proteins in cells with or without DN R-Ras expression were differentially labeled with SILAC and mass spectrometry was used to identify phosphoproteins and determine their relative quantities in the presence and absence of DN R-Ras. (biomedcentral.com)
  • Both proteins were activated in neurofibromin-null MPNST cells. (biomedcentral.com)
Domains2
  • Pleckstrin is one of the rare proteins to contains two PH domains. (embl.de)
  • There are 196127 PH domains in 171590 proteins in SMART's nrdb database. (embl.de)
Source5
Major1
  • Pleckstrin, the protein where this domain was first detected, is the major substrate of protein kinase C in platelets. (embl.de)
Multiple1
  • The domain family possesses multiple functions including the abilities to bind inositol phosphates, and various proteins. (embl.de)
Alpha1
Highly1
  • The RAS family consists of three proteins all sharing a highly conserved N-terminus region: Harvey RAS (HRAS), Kirsten RAS (KRAS) and neuroblastoma RAS (NRAS). (biomedcentral.com)