• Downstream signalling is controlled by both RAS-intrinsic GTP hydrolysis, guanine nucleotide exchange factors (GEFs) that catalyse hydrolysis and GTPase-activating proteins (GAPs) [ 2 ]. (biomedcentral.com)
  • 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)
  • Can activate specifically hydrolysis of GTP bound to RAC1 and CDC42, but not RALA. (innatedb.com)
  • GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude. (umbc.edu)
  • The fact that the RBD region of Rhotekin has a high affinity for GTP-RhoA and that Rhotekin binding results in a significantly reduced intrinsic and catalytic rate of GTP hydrolysis make it an ideal tool for affinity purification of GTP-RhoA from cell lysates. (cytoskeleton.com)
  • They associate with microtubule bundles (MICROTUBULES) and are believed to produce mechanical force via a process linked to GTP hydrolysis. (lookformedical.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)
  • 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)
  • 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)
  • HLB1 Is a Tetratricopeptide Repeat Domain-Containing Protein That Operates at the Intersection of the Exocytic and Endocytic Pathways at the TGN/EE in Arabidopsis. (ouhsc.edu)
  • 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)
  • 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)
  • 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)
  • This protein is one of two paralogs of the Ral protein, the other being RalA, and part of the Ras GTPase family. (wikipedia.org)
  • As a Ras GTPase, RalB functions as a molecular switch that becomes active when bound to GTP and inactive when bound to GDP. (wikipedia.org)
  • Ras is a small GTPase that operates as a binary molecular switch between a GDP-bound inactive and GTP-bound active state. (rupress.org)
  • The activation process is executed by guanine nucleotide exchange factors, while inactivation is mediated by GTPase-activating proteins (GAPs). (bvsalud.org)
  • RhoGap_RalBP1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain present in RalBP1 proteins, also known as RLIP, RLIP76 or cytocentrin. (umbc.edu)
  • RalBP1 is an effector of the Ral GTPase which itself is an effector of Ras. (umbc.edu)
  • 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)
  • 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)
  • 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)
  • RalB is one of two proteins in the Ral family, which is itself a subfamily within the Ras family of small GTPases. (wikipedia.org)
  • Ral GTPases are activated downstream of Ras and play a crucial role in the development and progression of PDAC. (bvsalud.org)
  • In this study, we investigated the mechanism of Ral-induced invasion and metastasis of PDAC cells using RalGAPß-deficient PDAC cells with highly activated Ral GTPases. (bvsalud.org)
  • Ras proteins are the founding members of the Ras superfamily of GTPases, which in humans is composed of more than 150 members [ 1 ] [ 2 ] . (encyclopedia.pub)
  • Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. (umbc.edu)
  • In primary mammalian cells oncogenic induces premature senescence depending on an active MEK-extracellular signal-regulated kinase (ERK) mitogen-activated protein kinase (MAPK) pathway. (molecularcircuit.com)
  • 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)
  • 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)
  • The fact that many Rho family effector proteins will specifically recognize the GTP bound form of the protein has been exploited experimentally to develop a powerful affinity purification assay that monitors RhoA protein activation. (cytoskeleton.com)
  • They share a common structure and signal through HETEROTRIMERIC G-PROTEINS. (lookformedical.com)
  • Moreover, RalB specifically interacts with Exo84 to assemble the beclin-1-VPS34 autophagy initiation complex, and with Sec5 to activate the innate immune response via the Tank-binding kinase 1 (TBK1). (wikipedia.org)
  • These results indicate that Ral contributes to invasion and metastasis of PDAC cells by elevating autocrine TGF-ß1 signaling at least in part by decreasing c-Jun N-terminal kinase activity. (bvsalud.org)
  • Pleckstrin, the protein where this domain was first detected, is the major substrate of protein kinase C in platelets. (embl.de)
  • A ubiquitously expressed G-protein-coupled receptor kinase subtype that has specificity for the agonist-occupied form of BETA-ADRENERGIC RECEPTORS and a variety of other G-PROTEIN-COUPLED RECEPTORS. (lookformedical.com)
  • Although it is highly homologous to G-PROTEIN-COUPLED RECEPTOR KINASE 2, it is not considered to play an essential role in regulating myocardial contractile response. (lookformedical.com)
  • A G-protein-coupled receptor kinase subtype that is primarily expressed in the MYOCARDIUM and may play a role in the regulation of cardiac functions. (lookformedical.com)
  • 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)
  • Ser/Thr protein kinases such as the Akt/Rac family, the beta-adrenergic receptor kinases, the mu isoform of PKC and the trypanosomal NrkA family. (embl.de)
  • Tyrosine protein kinases belonging to the Btk/Itk/Tec subfamily. (embl.de)
  • A family of serine-threonine kinases that are specific for G-PROTEIN-COUPLED RECEPTORS. (lookformedical.com)
  • Ral proteins are found in GTP-bound active and GDP-bound inactive forms. (bvsalud.org)
  • 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)
  • The Rho switch operates by alternating between an active, GTP-bound state and an inactive, GDP-bound state. (cytoskeleton.com)
  • While the above functions appear to be shared between the two Ral isoforms, their differential subcellular localizations result in their differing involvement in certain biological processes. (wikipedia.org)
  • Several isoforms of the protein with molecular sizes of 47 kDa and 52 kDa exist due to multiple ALTERNATIVE SPLICING. (lookformedical.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)
  • Ras proteins regulate cell growth, proliferation and differentiation. (umbc.edu)
  • 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)
  • Regulatory proteins that down-regulate phosphorylated G-protein membrane receptors, including rod and cone photoreceptors and adrenergic receptors. (lookformedical.com)
  • 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)
  • 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)
  • 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)
  • 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)
  • Lipid binding is essential for membrane attachment, a key feature of most Ras proteins. (umbc.edu)
  • The proto-oncogene family members encodes little GTP binding proteins that transduce development indicators from cell surface area receptors in response to extracellular stimuli (1 6 37 Prior studies have recommended that aberrant activation of is certainly a crucial stage during tumorigenesis. (molecularcircuit.com)
  • 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)
  • A family of G-protein-coupled receptors that was originally identified by its ability to bind N-formyl peptides such as N-FORMYLMETHIONINE LEUCYL-PHENYLALANINE. (lookformedical.com)
  • 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)
  • 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)
  • Clathrin also interacts with cytoskeletal proteins. (lookformedical.com)
  • Serves as a scaffold protein that brings together proteins forming an endocytotic complex during interphase and also with CDK1 to switch off endocytosis, One of its substrates would be EPN1/Epsin (By similarity). (innatedb.com)
  • 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)
  • When ARF family proteins are activated, they bind to effector molecules, which in turn mediate downstream functions. (biomedcentral.com)
  • Eye proteins are the biological molecules that make up the various structures of the eye and are essential for its proper function. (lookformedical.com)
  • Ras-related protein Ral-B (RalB) is a protein that in humans is encoded by the RALB gene on chromosome 2. (wikipedia.org)
  • What does this gene/protein do? (cancerindex.org)
  • This gene and/or its encoded proteins are associated with 5 experimentally validated interaction(s) in this database. (innatedb.com)
  • Oncogenic RAS expression increased S100A10 gene expression which resulted in an increase in S100A10 protein levels. (oncotarget.com)
  • RalBP1 contains a RhoGAP domain, which shows weak activity towards Rac1 and Cdc42, but not towards Ral, and a Ral effector domain binding motif. (umbc.edu)
  • In contrast, highly toxic alpha-strain-based N501Y substitution strongly bound to platelets in a RGD dependent manner, although binding of S protein did not induce platelet aggregation or activation. (bvsalud.org)
  • 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)
  • Here, we examined the expression, activation and action of R-Ras proteins in MPNST cells that have lost neurofibromin. (biomedcentral.com)
  • The RhoA activation assay was tested by loading the RhoA protein in cell lysates with either GTPγS or GDP. (cytoskeleton.com)
  • Arrestin quenches G-protein activation by binding to phosphorylated photolyzed rhodopsin. (lookformedical.com)
  • The main structural coat protein of COATED VESICLES which play a key role in the intracellular transport between membranous organelles. (lookformedical.com)
  • 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)
  • The process of moving proteins from one cellular compartment (including extracellular) to another by various sorting and transport mechanisms such as gated transport, protein translocation, and vesicular transport. (lookformedical.com)
  • 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)
  • SARS-CoV-2 enters host cells through association of the spike protein (S-protein) with its receptor, angiotensin-converting enzyme 2 (ACE-2), on the host cells. (bvsalud.org)
  • We generated RalGAPß-deficient PDAC cells by CRISPR-Cas9 genome editing to investigate how increased Ral activity affects malignant phenotypes of PDAC cells. (bvsalud.org)
  • RalGAPß-deficient PDAC cells exhibited several-fold higher Ral activity relative to control cells. (bvsalud.org)
  • 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)
  • 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)
  • 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 have shown that classic Ras proteins promote proliferation and survival, but not migration, in malignant peripheral nerve sheath tumor (MPNST) cells. (biomedcentral.com)
  • 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)
  • The Rhotekin-RBD protein supplied in this kit contains Rhotekin residues 7-89 and is in the form of a GST fusion protein, which allows one to "pull-down" the Rhotekin-RBD/Rho-GTP complex with brightly colored glutathione affinity beads. (cytoskeleton.com)
  • 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)
  • Mass spectrometry-based phosphoproteomics identified thirteen protein networks distinctly regulated by DN R-Ras, including multiple networks regulating cellular movement and morphology. (biomedcentral.com)
  • 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)
  • Sara B.-M. Whittaker Understanding the mechanism of folding of small proteins requires characterization of their starting unfolded states and any partially unfolded states populated during folding. (silverchair.com)
  • Pleckstrin homology (PH) domains are small modular domains that occur in a large variety of proteins. (embl.de)
  • The concept of the validation cross was originally introduced for the validation of protein-ligand interactions by NMR in drug discovery. (silverchair.com)
  • 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)
  • The RBD motif has been shown to bind specifically to the GTP-bound form of RhoA. (cytoskeleton.com)
  • This group of proteins is responsible for cell proliferation, differentiation and inhibition of apoptosis. (biomedcentral.com)
  • Their C-terminal EVH2 domain mediates tetramerization and binds both G and F actin. (antibodies-online.com)
  • While presence of ACE2 in platelets is suspicious, S-protein harbors the RGD sequences within its receptor binding domain. (bvsalud.org)
  • Therefore, it could be possible SARS-CoV-2 enter platelets through association of S-protein with αIIbß3. (bvsalud.org)
  • In this study, we found that receptor binding domain of S-protein of WT SARS-CoV-2 strain barely bound to isolated healthy human platelets. (bvsalud.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)
  • Several S. cerevisiae proteins involved in cell cycle regulation and bud formation like BEM2, BEM3, BUD4 and the BEM1-binding proteins BOI2 (BEB1) and BOI1 (BOB1). (embl.de)
  • RBD, Ras-binding domain of Raf-1. (rupress.org)
  • The SEM-5 (Grb2) adaptor protein 11 uses its SH2 domain to anchor to LET-23 at phosphorylated tyrosines. (hideyuki-ts.com)
  • If you've navigated here from a protein, hovering over a position on the weblogo will display the corresponding protein position for that domain position. (umbc.edu)
  • The assay uses the Rho binding domain (RBD) of the Rho effector protein, Rhotekin. (cytoskeleton.com)
  • Domain commonly found in eukaryotic signalling proteins. (embl.de)
  • Taxonomic distribution of proteins containing PH domain. (embl.de)
  • The complete taxonomic breakdown of all proteins with PH domain is also avaliable . (embl.de)
  • Click on the protein counts, or double click on taxonomic names to display all proteins containing PH domain in the selected taxonomic class. (embl.de)