• Ras is the prototypical member of the Ras superfamily of proteins, which are all related in three-dimensional structure and regulate diverse cell behaviours. (wikipedia.org)
  • RAS proteins are the founding members of the RAS superfamily of GTPases. (oncotarget.com)
  • The superfamily of GTP binding proteins, of which Ras proteins are prototypes, has been implicated in a broad range of biological activities. (ihcworld.com)
  • Ras-GRF p140 promotes nucleotide exchange on Ras p21s but not on other members of the Ras gene superfamily. (ihcworld.com)
  • RAS is a founding member of the RAS superfamily of GTPases. (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)
  • The Ras superfamily of small GTPases is perhaps best known for linking external mitogenic stimuli to internal signal transduction pathways, leading to changes in gene expression affecting cell proliferation and survival. (biomedcentral.com)
  • The products of these genes can be conveniently (but not always accurately) lumped into four sub-families of the Ras superfamily: the Ras, Rab, Rho, and Arf proteins. (nih.gov)
  • The Ras superfamily comprises many guanine nucleotide-binding proteins (G proteins) that are essential to intracellular signal transduction. (irbbarcelona.org)
  • 2023. Optogenetic modulation of guanine nucleotide exchange factors of Ras superfamily proteins directly controls cell shape and movement. (jhmi.edu)
  • Guanine Nucleotide Exchange Factors: Activators of the Ras Superfamily of Proteins.Lawrence A. Quilliam, Roya Khosravi-Far, Shayne Y. Huff & Channing J. (namenfinden.de)
  • This gene encodes a member of the Ras superfamily of small guanosine triphosphate (GTP)-metabolizing proteins. (nih.gov)
  • Another Ras-activated signaling pathway is the PI3K/AKT/mTOR pathway, which stimulates protein synthesis and cellular growth, and inhibits apoptosis. (wikipedia.org)
  • 6. A novel human STE20-related protein kinase, HGK, that specifically activates the c-Jun N-terminal kinase signaling pathway. (nih.gov)
  • 15. JSAP1, a novel jun N-terminal protein kinase (JNK)-binding protein that functions as a Scaffold factor in the JNK signaling pathway. (nih.gov)
  • The SOS1 gene provides instructions for making a protein that is involved in controlling (regulating) the activation of the RAS/MAPK signaling pathway, which helps control several important cell functions. (medlineplus.gov)
  • Within the RAS/MAPK signaling pathway, the SOS1 protein regulates a protein, called Ras, that stimulates cells to grow and divide. (medlineplus.gov)
  • This increase in protein activity disrupts the regulation of the RAS/MAPK signaling pathway that controls cell functions such as growth and division. (medlineplus.gov)
  • These ATG proteins also perform an important parallel role in 'noncanonical' autophagy, a lysosome-associated signaling pathway with key functions in immunity, inflammation, cancer, and neurodegeneration. (babraham.ac.uk)
  • Ras activates several pathways, of which the mitogen-activated protein (MAP) kinase cascade has been well-studied. (wikipedia.org)
  • 11. Guanine-nucleotide exchange protein C3G activates JNK1 by a ras-independent mechanism. (nih.gov)
  • 19. MST/MLK2, a member of the mixed lineage kinase family, directly phosphorylates and activates SEK1, an activator of c-Jun N-terminal kinase/stress-activated protein kinase. (nih.gov)
  • cAMP is converted via adenylyl cyclase (AC) and activates protein kinase A to phosphorylate intracellular proteins that mediate specific responses. (spandidos-publications.com)
  • 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)
  • The data suggest that overexpression of RasGRF1 activates signal transduction pathways that target the MMP-3 gene, thereby contributing to joint destruction in RA. (biomedcentral.com)
  • This gene encodes a DENN domain-containing protein that may function as a guanine nucleotide exchange factor that specifically activates ras-related protein Rab-10. (utsouthwestern.edu)
  • GTP binding activates and GTP hydrolysis inactivates RAS proteins. (platcovid.com)
  • 13. Evidence for a role of Rho-like GTPases and stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) in transforming growth factor beta-mediated signaling. (nih.gov)
  • From NCBI Gene: RAS GTPases cycle between an inactive GDP-bound state and an active GTP-bound state. (nih.gov)
  • Ras proteins are signal-transducing GTPases that cycle between inactive GDP- bound and active GTP-bound forms. (embl-heidelberg.de)
  • A domain of about 100 residues, termed RA for RalGDS/AF-6 or Ras-Associating, interacts with Ras and other small GTPases. (embl-heidelberg.de)
  • The RAS protein family is a set of small GTPases that function as binary switches by alternating their activation state from GTP-bound (active) to GDP-bound (inactive). (oncotarget.com)
  • Rho guanine-nucleotide exchange factors (RhoGEFs) activate Rho GTPases, and thereby regulate cytoskeletal structure, gene transcription, and cell migration. (rcsb.org)
  • Nucleotide binding switches the information flow in ras GTPases. (irbbarcelona.org)
  • As the most well-known members, Ras GTPases play essential roles in regulating cell growth, cell differentiation, cell migration, and lipid vesicle trafficking. (digglicious.com)
  • GTP-binding proteins belong to two families: heterotrimeric G proteins see Transducin and small GTPases. (digglicious.com)
  • Mutations in Ras genes can lead to the production of permanently activated Ras proteins, which can cause unintended and overactive signaling inside the cell, even in the absence of incoming signals. (wikipedia.org)
  • mutations that permanently activate Ras are found in 20 to 25% of all human tumors and up to 90% in certain types of cancer (e.g., pancreatic cancer). (wikipedia.org)
  • Mutations in the three closely related ras genes, H-ras, K-ras, and N-ras, are among the most common mutations found in human cancer, reaching 50% in some types of tumors, such as colorectal carcinoma. (cyberessays.com)
  • Mutations of the K-Ras gene occur in over 90% of pancreatic carcinomas. (cyberessays.com)
  • Most mutations in genes are expected to cause their inactivation, however, in the Ras genes the opposite happens - they become more active in signaling. (cyberessays.com)
  • In reality, the mutations of Ras do indeed inactivate a function, as most mutations are expected to do. (cyberessays.com)
  • Ras mutations involve only certain amino acids, those which interfere with the GTPase function. (cyberessays.com)
  • The mutation to serine is quite unusual in pancreatic cancer, a peculiar finding since it is a common mutation in other tumor types which have K-ras mutations. (cyberessays.com)
  • Mutations in K-ras occur early in the development of colon carcinoma. (cyberessays.com)
  • 1998) and are discussed in relation to partial loss-of-function mutations and the specificity of Ras versus Rap binding. (embl-heidelberg.de)
  • The RAS gene family ( KRAS , NRAS , and HRAS ) comprises the most common oncogenes in cancer, with mutations in KRAS being prevalent in three of the most lethal cancers (lung cancer, colorectal cancer, and pancreatic cancer). (nih.gov)
  • The SOS1 gene mutations change single protein building blocks (amino acids) in the SOS1 protein. (medlineplus.gov)
  • KRAS, a membrane-bound guanine nucleotide-binding protein, is the most frequently mutated oncogene in human cancer, with mutations detected in ∼30% of all tumors. (aacrjournals.org)
  • This gene encodes a calcium-regulated nucleotide exchange factor activating both RAS and RAS-related protein, RAC1, through the exchange of bound GDP for GTP, thereby, coordinating the signaling of distinct mitogen-activated protein kinase pathways. (nih.gov)
  • These results reveal a potential mechanism for coupling of Ras and Rac signaling pathways. (embl.de)
  • In higher eukaryotes these proteins are involved in signal transduction pathways controlling a diverse array of essential cellular functions, such as growth, differentiation and survival [ 1 ]. (oncotarget.com)
  • In eukaryotic cells, protein transport through the secretory and endocytic pathways is mediated by vesicular intermediates. (embl.de)
  • Although these similarities have been noted for at least 30 years at a phenotypic level [ 2 ], we are now shedding light on their molecular basis (for example, changes in the expression of tumor suppressor proteins and oncogenes and the activation of certain mitogen-activated protein kinase signal transduction pathways) [ 4 , 5 ]. (biomedcentral.com)
  • and phosphoinositide (PI) 3′-kinase and Ral-guanine nucleotide dissociation stimulator (Ral-GDS) which activate lipid pathways (2). (ecologicalsgardens.com)
  • In some pathological conditions, axonal degeneration does not employ the standard apoptotic pathways, and instead involves the SARM1 protein, which induces axonal degeneration in response to various insults, and is therefore considered an attractive drug target for the treatment of neuro-degenerative diseases as well as for brain and spinal cord injuries. (opatowskylab.com)
  • Thus, modulation of protein clearance pathways is a promising approach for therapeutics. (springer.com)
  • Misfolded proteins that ensue from external and internal stressors are degraded through two major protein clearance pathways, i.e., the ubiquitin-proteasome system (UPS) and the autophagy-lysosome pathway. (springer.com)
  • Raf kinase inhibitor protein (RKIP) is a member of the phosphatidylethanolamine-binding protein (PEBP) family that interacts with a number of different proteins and regulates multiple signaling pathways. (axonmedchem.com)
  • Although the pathogenic pathways involved in IPF have not been fully elucidated, IPF is believed to be caused by repetitive alveolar epithelial cell injury and dysregulated repair, in which there is uncontrolled proliferation of lung fibroblasts and differentiation of fibroblasts into myofibroblasts, which excessively deposit extracellular matrix (ECM) proteins in the interstitial space. (ersjournals.com)
  • This gene encodes a protein that is a guanine nucleotide exchange factor for RAS proteins, membrane proteins that bind guanine nucleotides and participate in signal transduction pathways. (platcovid.com)
  • SynGAP binds to PSD95 and is enriched at synapses where it regulates ras, thereby controlling glutamatergic signaling via extracellular signal-regulated protein kinase (ERK) and p38 MAP kinase pathways. (digglicious.com)
  • We then analyzed how genotoxic stressors may promote the release of IGFBP-4 and the molecular pathways associated with the induction of senescence by this protein. (elifesciences.org)
  • The aim is to evaluate the association between high myopia and genetic variant in the BicC family RNA binding protein 1 (BICC1) as well as its association with Ras protein specific guanine nucleotide releasing factor 1 (RASGRF1) genes in a Chinese Han population with a case-control study. (nih.gov)
  • When Ras is 'switched on' by incoming signals, it subsequently switches on other proteins, which ultimately turn on genes involved in cell growth, differentiation, and survival. (wikipedia.org)
  • The first two Ras genes, HRAS and KRAS, were identified from studies of two cancer-causing viruses, the Harvey sarcoma virus and Kirsten sarcoma virus, by Edward M. Scolnick and colleagues at the National Institutes of Health (NIH). (wikipedia.org)
  • In 1982, activated and transforming human ras genes were discovered in human cancer cells by Geoffrey M. Cooper at Harvard, Mariano Barbacid and Stuart A. Aaronson at the NIH, Robert Weinberg at MIT, and Michael Wigler at Cold Spring Harbor Laboratory. (wikipedia.org)
  • The three human ras genes encode extremely similar proteins made up of chains of 188 to 189 amino acids. (wikipedia.org)
  • The Saccharomyces cerevisiae CDC25 gene and closely homologous genes in other eukaryotes encode guanine nucleotide exchange factors for Ras proteins. (cshl.edu)
  • In the human genome, the RAS family includes a large number of related genes (paralogs). (oncotarget.com)
  • In addition to measuring MMP-3 expression, they measured levels of the interstitial collagenase, MMP-1, and several other genes involved in RA. (biomedcentral.com)
  • In the ensuing years, the number of distinct genes discovered that encode low-molecular-weight GTP-binding proteins has increased to more than 100. (nih.gov)
  • In the online version, these sections contain links to more information about proteins encoded by over 17,000 known or predicted human genes. (cshlpress.com)
  • 7. Regulation of c-Jun N-terminal kinase by MEKK-2 and mitogen-activated protein kinase kinase kinases in rheumatoid arthritis. (nih.gov)
  • Mammalian Ras proteins regulate multiple effectors including Raf, Ral guanine nucleotide dissociation stimulator (RalGDS), and phosphoinositide 3-kinase. (embl-heidelberg.de)
  • Unlike the normal SOS1 protein, the shortened protein is permanently active because it is missing areas that regulate its activity. (medlineplus.gov)
  • These proteins, called ADP-ribosylation factors, or Arfs, have recently been found to 1) interact with specific lipid components of membranes, 2) modify the lipid composition and release potential second messengers through activation of phospholipase D (PLD), and 3) regulate the assembly of at least a subset of protein complexes or membrane coats (for reviews, see refs. (nih.gov)
  • The product of this gene may regulate RAS proteins by facilitating the exchange of GTP for GDP. (platcovid.com)
  • GTPase-activating proteins (GAPs) regulate heterotrimeric G proteins by increasing the rates at which their subunits hydrolyze bound GTP and thus return to the inactive state. (digglicious.com)
  • GTPase proteins regulate a variety of cellular processes, including membrane trafficking in cells (Stenmark, 2009). (digglicious.com)
  • Proteins that regulate vesicle exocytosis cluster at AZs, composing the cytomatrix at the active zone (CAZ). (eneuro.org)
  • A yeast gene encoding a protein homologous to the human c-has/bas proto-oncogene product. (embl.de)
  • In a recent issue of Arthritis Research & Therapy , Abreu and colleagues link a well-studied oncogene, Ras, with expression of matrix metalloproteinase-3 (MMP-3) in RA. (biomedcentral.com)
  • In the present study, the parallel between RA and cancer is further demonstrated by Ras, a classic oncogene, as a signaling molecule in RA fibroblast-like synoviocytes. (biomedcentral.com)
  • This protein also contains a interferon stimulated response element-binding domain and may be involved in regulating the v-myc avian myelocytomatosis viral (MYC) oncogene. (utsouthwestern.edu)
  • Dephosphorylation of tyrosine 393 in argonaute 2 by protein tyrosine phosphatase 1B regulates gene silencing in oncogenic RAS-induced senescence. (nih.gov)
  • In a recent issue of Arthritis Research & Therapy , Abreu and colleagues [ 1 ] demonstrate that the Ras guanine nucleotide exchange factor (GEF) RasGRF1 regulates production of matrix metalloproteinase-3 (MMP-3) (stromelysin) in synovial cells taken from the joints of patients with rheumatoid arthritis (RA). (biomedcentral.com)
  • The encoded protein localizes to the plasma membrane, where it regulates diverse processes, such as secretion, phagocytosis, and cell polarization. (nih.gov)
  • The V-ATPase complex regulates non-canonical Atg8-family protein lipidation through ATG16L1 recruitment. (babraham.ac.uk)
  • Rlf is a guanine nucleotide exchange factor for the small G-proteins RalA and RalB and couples Ras- to Ral-signalling. (rcsb.org)
  • GEFs, GAPs, GDIs and effectors: taking a closer (3D) look at the regulation of Ras-related GTP-binding proteins. (embl.de)
  • To search for other effectors in C. elegans, we performed a yeast two-hybrid screening for LET-60-binding proteins. (embl-heidelberg.de)
  • We found specific conserved amino acid positions in this group that map to the binding sites of RAS with many of their signaling effectors, suggesting that these pairs could share interacting partners. (oncotarget.com)
  • Recent findings, however, indicate that their function in vesicle trafficking can go beyond this role, and a number of proteins, unrelated to each other, have been identified as putative Rab effectors. (embl.de)
  • Upstream signaling events activate GEFs, which mediate the exchange of GDP (on inactive Ras) for GTP, thus causing a conformational change to an active state and interaction with downstream effectors. (biomedcentral.com)
  • They are bona fide Ras (a membrane-associated guanine nucleotide-binding protein) effectors and upstream activators of the ubiquitous ERK pathway , which has drawn the attention to these proteins as potential targets in cancer therapy . (axonmedchem.com)
  • 18. Requirement of TGF-beta receptor-dependent activation of c-Jun N-terminal kinases (JNKs)/stress-activated protein kinases (Sapks) for TGF-beta up-regulation of the urokinase-type plasminogen activator receptor. (nih.gov)
  • cAMP and cGMP are important secondary messengers involved in cell regulation and metabolism driven by the G protein‑coupled receptor. (spandidos-publications.com)
  • 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)
  • They elucidate a potential mechanism of regulation of MMP-3 expression in RA, suggesting a potential target for RA treatment. (biomedcentral.com)
  • Chan, E. Y. (2012) Regulation and Function of Uncoordinated-51 Like Kinase Proteins. (edmondchanlab.com)
  • CR2 contains important inhibitory phosphorylation sites participating in the negative regulation of Ras binding and Raf activation. (axonmedchem.com)
  • SRC is implicated in regulation of pre-mRNA-processing and phosphorylates RNA-binding proteins such as KHDRBS1. (drugbank.com)
  • However, the Atg8 family of proteins are not found solely attached to double-membrane autophagosomes. (babraham.ac.uk)
  • This conformational change by the two switch motifs is what mediates the basic functionality as a molecular switch protein. (wikipedia.org)
  • Ras proteins function as binary molecular switches that control intracellular signaling networks. (wikipedia.org)
  • Ras proteins are membrane-associated molecular switches that bind GTP and GDP and slowly hydrolyze GTP to GDP [ ( PUBMED:1898771 ) ] in fundamental events such as signal transduction, cytoskeleton dynamics and intracellular trafficking. (embl.de)
  • The ras signal is turned off by a molecular switch, which depends on an enzyme activity. (cyberessays.com)
  • These small 21 kDa proteins function as molecular switches to initialize signaling cascades involved in various cellular processes, including gene expression, cell growth, and differentiation. (nih.gov)
  • Some portray biological membranes as molecular putty readily fashioned into different shapes (vesicles, tubes, and sheets) by proteins or protein complexes. (nih.gov)
  • The guanine nucleotide-dependent intrinsic flexibility patterns of five G proteins were investigated in atomic detail through Molecular Dynamics simulations of the GDP- and GTP-bound states (S(GDP) and S(GTP), respectively). (irbbarcelona.org)
  • These docking protein build a molecular scaffold that subsequent indicators emanate. (ecologicalsgardens.com)
  • Ras serves as a molecular switch in the plasma membrane that alternates between an inactive GDP-bound state and an active GTP-bound state. (ecologicalsgardens.com)
  • G proteins are molecular switches that are activated by receptor-catalyzed GTP for GDP exchange on the G protein alpha subunit, which is the rate-limiting step in the activation of all downstream signaling. (digglicious.com)
  • Our studies reveal that Rab3 and Rab3-GEF act within the same molecular mechanism and support a model wherein Rab3-GEF serves as a Rab3 effector to control active zone protein composition. (eneuro.org)
  • RT "Molecular characterization of the interferon-induced 15-kDa protein. (pdbj.org)
  • RT Molecular cloning and nucleotide and amino acid sequence. (pdbj.org)
  • Ras is a prolific signalling molecule interacting with a spectrum of effector molecules and acting through more than one signalling pathway. (embl-heidelberg.de)
  • Structural and biochemical analysis of Ras-effector signaling via RalGDS. (embl-heidelberg.de)
  • The structure of the complex of Ras with the Ras-binding domain of its effector RalGDS (RGS-RBD), the first genuine Ras-effector complex, has been solved by X-ray crystallography. (embl-heidelberg.de)
  • Identification of PLC210, a Caenorhabditis elegans phospholipase C, as a putative effector of Ras. (embl-heidelberg.de)
  • In the nematode Caenorhabditis elegans, LIN-45 Raf has been identified by genetic analyses as an effector of LET-60 Ras. (embl-heidelberg.de)
  • This includes developing non-traditional screening approaches for formerly undruggable targets and has broadened the scope of RAS-directed therapies to include multiple RAS alleles as well as RAS regulatory and effector proteins. (nih.gov)
  • For all the considered systems, the intrinsic flexibility of S(GDP) was higher than that of S(GTP), suggesting that Guanine Exchange Factor (GEF) recognition and nucleotide switch require higher amplitude motions than effector recognition or GTP hydrolysis. (irbbarcelona.org)
  • Ras-GTP adopts a conformation that permits conversation with downstream targets called effector molecules. (ecologicalsgardens.com)
  • RT "The interferon-inducible 15-kDa ubiquitin homolog conjugates to RT intracellular proteins. (pdbj.org)
  • This dominantly acting mutation in ras results in its constitutive activation and. (cyberessays.com)
  • This mutation is an addition of a single building block of DNA (nucleotide). (medlineplus.gov)
  • The mutation inserts the nucleotide cytosine into an area of the gene called exon 21 (written 3248_3249insC) and disrupts the gene's instructions, resulting in a shortened protein. (medlineplus.gov)
  • Additionally, the spike proteins of these sarbecoviruses possess an R-A-K-Q motif, which lies only one nucleotide mutation away from a furin cleavage site (FCS) that enhances infectivity in other coronaviruses, including SARS-CoV-2. (nature.com)
  • The level of cAMP is increased in association with cancer cell formation through activation of AC‑stimulatory G protein by mutation. (spandidos-publications.com)
  • For example the guanine nucleotide exchange factor Sos binds to Grb2 which in turn interacts with the Ras protein. (ecologicalsgardens.com)
  • When expressed in Escherichia coli as a fusion protein, this region of CDC25 was found to be a potent catalyst of GDP-GTP exchange on yeast Ras2 as well as human p21H-ras but inactive in promoting exchange on the Ras-related proteins Ypt1 and Rsr1. (cshl.edu)
  • Functional mode, dynamic domain, and interaction energy correlation analyses highlighted significant differences in the dynamics of small G proteins and Gα proteins, especially in the inactive state. (irbbarcelona.org)
  • Finally, in small G proteins, functional modes are more detectable in the inactive state than in the active one and involve changes in solvent exposure of two highly conserved amino acids in switches I and II involved in GEF recognition. (irbbarcelona.org)
  • These proteins act as switches by alternating between an active, GTP-bound state and an inactive, GDP-bound state. (digglicious.com)
  • This GTP-bound state of Ras is the "on" state, and the GDP-bound state is the "off" state. (wikipedia.org)
  • The two switch motifs have a number of conformations when binding GTP or GDP or no nucleotide (when bound to SOS1, which releases the nucleotide). (wikipedia.org)
  • The CDC25 fusion protein catalyzed replacement of GDP-bound to Ras2 with GTP (activation) more efficiently than that of the reverse reaction of replacement of GTP for GDP (deactivation), consistent with prior genetic analysis of CDC25 which indicated a positive role in the activation of Ras. (cshl.edu)
  • This higher affinity of CDC25 for the nucleotide-free form than for either the GDP- or GTP-bound form suggests that CDC25 catalyzes exchange of guanine nucleotides bound to Ras proteins by stabilization of the transitory nucleotide-free state. (cshl.edu)
  • GTP-bound Ras is inactivated by its intrinsic GTPase capability, which hydrolyzes GTP to GDP, and is aided by GTPase-activating proteins that stimulate the GTPase activity [ 3 ]. (biomedcentral.com)
  • Normally Ras is bound to GDP because of the abundance of GTPase-activating protein and neurofibromin which both suppress Ras function. (ecologicalsgardens.com)
  • A GTPase activity intrinsic to the G-protein cleaves bound GTP to GDP. (digglicious.com)
  • Thus in the "basal" state, G-proteins contain tightly bound GDP. (digglicious.com)
  • Association of G-protein with an activated receptor (a receptor to which an agonist ligand has bound) leads to release of bound GDP. (digglicious.com)
  • Studies have identified a family of guanine nucleotidereleasing factors (GRFs) that activate Ras in mammalian cells and an 'adapter' protein (Sem 5/GRB2) that appears to mediate the interaction of GRFs with activated receptor molecules. (ihcworld.com)
  • Does GTP activate G protein? (digglicious.com)
  • This analysis was integrated with the structural analysis of conserved positions in available 3D structures of RAS complexes. (oncotarget.com)
  • Ras and Ras-related proteins are often deregulated in cancers, leading to increased invasion and metastasis, and decreased apoptosis. (wikipedia.org)
  • Flickinger RA , Protein kinase activity, growth and differentiation of murine erythroleukemia cells. (coriell.org)
  • The ras-related ypt protein is an ubiquitous eukaryotic protein: isolation and sequence analysis of mouse cDNA clones highly homologous to the yeast YPT1 gene. (embl.de)
  • The YPT1 gene of the yeast Saccharomyces cerevisiae codes for a guanine nucleotide-binding protein which is essential for cell viability. (embl.de)
  • The cDNAs were derived from a gene, designated ypt1, which codes for a protein of 205 amino acids with 71% homology to the yeast YPT1 gene product. (embl.de)
  • Amino acid sequences typical for guanine nucleotide-binding proteins and characteristic for ypt proteins are perfectly conserved in the mouse ypt1 protein. (embl.de)
  • Two mRNAs of 1600 and 3200 nucleotides, originating from the mouse ypt1 gene and differing in the length of their 3'-non-translated region, were identified in mouse F9 cells and in all mouse tissues examined. (embl.de)
  • A monoclonal antibody specifically recognizing the 23.5-kd yeast YPT1 protein cross-reacted with a protein of identical size on protein blots of mouse, rat, pig, bovine and human cell lines. (embl.de)
  • Violin plots show distribution of expression levels for Ras-like GTP-binding protein YPT1 (SMED30004913) in cells (dots) of each of the 12 neoblast clusters. (stowers.org)
  • Expression of Ras-like GTP-binding protein YPT1 (SMED30004913) in the t-SNE clustered sub-lethally irradiated X1 and X2 cells. (stowers.org)
  • In addition, three mammalian homologs of the Drosophila Ras-GRF, son of sevenless (Sos), have been described. (ihcworld.com)
  • Localization of Arf proteins to the cytosolic side of (predominantly) cis -Golgi structures, and later other Golgi-related structures, further supports the conclusion that a major site of Arf action in mammalian cells is the Golgi complex. (nih.gov)
  • The proteome of a mammalian cell contains thousands of distinct proteins (Jayaraj et al. (springer.com)
  • As the Drosophila homologue of mammalian DENN/MADD and Caenorhabditis elegans AEX-3, Rab3-GEF is a guanine nucleotide exchange factor (GEF) for Rab3 that stimulates GDP to GTP exchange. (eneuro.org)
  • With the exception of the relatively well-known KRAS, HRAS and NRAS proteins, little is known about how the interactions of the other RAS human paralogs affect cancer evolution and response to treatment. (oncotarget.com)
  • For this reason, Ras inhibitors are being studied as a treatment for cancer and other diseases with Ras overexpression. (wikipedia.org)
  • 3. Continue to catalyze the renaissance in RAS targeting approaches on a global scale, including efforts to understand the dynamics of RAS activation, and explore inhibitors of additional RAS family members. (nih.gov)
  • This notion changed following discussions led by Dr. Varmus with NCI and extramural cancer community leaders, who pointed out that new chemical approaches were being developed in industry and academia that renewed interest in targeting RAS, with an initial focus on KRAS. (nih.gov)
  • 4. Interaction of hematopoietic progenitor kinase 1 with adapter proteins Crk and CrkL leads to synergistic activation of c-Jun N-terminal kinase. (nih.gov)
  • 16. Involvement of extracellular signal-regulated kinase 2 and stress-activated protein kinase/Jun N-terminal kinase activation by transforming growth factor beta in the negative growth control of breast cancer cells. (nih.gov)
  • The tandem DH-PH domain of Sos (DH-PH-Sos) was defective in Rac activation but regained Rac stimulating activity when it was coexpressed with activated Ras. (embl.de)
  • Ras-mediated activation of DH-PH-Sos did not require activation of mitogen-activated protein kinase but it was dependent on activation of phosphoinositide 3-kinase. (embl.de)
  • The resulting protein is either continuously turned on (active) or has prolonged activation, rather than promptly switching on and off in response to other cellular proteins. (medlineplus.gov)
  • Subsequent to activation, Ras appears to functionally interact with Raf, thereby activating the MAP kinase phosphorylation pathway. (ihcworld.com)
  • 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)
  • RasGRF1 is a guanine exchange factor with selectivity for H-, K-, N- and R-Ras, which mediates Ras isoform activation under a variety of conditions and has been associated with multiple diseases (reviewed in 1, 2). (cytoskeleton.com)
  • The common and key step in the activation of all 3 Raf isoforms is membrane recruitment by a Ras family protein. (axonmedchem.com)
  • Activation of G proteins is enabled by accessory proteins which catalyse guanine nucleotide exchange-the sequential release of GDP and binding of GTP. (digglicious.com)
  • SRC appears to be one of the primary kinases activated following engagement of receptors and plays a role in the activation of other protein tyrosine kinase (PTK) families. (drugbank.com)
  • The longest isoforms of PDE11A in the mouse and human share ~95% protein sequence homology. (spandidos-publications.com)
  • The biological activity of RasGRF1 CDC25 domain can be determined from its ability to catalyze nucleotide exchange on Ras isoforms using the nucleotide exchange assay of Bodipy-GDP for excess GDP or GTP. (cytoskeleton.com)
  • Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease whose hallmark feature is a persistent symmetric polyarthritis (synovitis) that affects the hands and feet (see the image below). (medscape.com)
  • See Rheumatoid Arthritis: In and Out of the Joint , a Critical Images slideshow, to help identify the distinguishing features of RA as well as the signs of extra-articular manifestations of this disfiguring disease. (medscape.com)
  • The shared characteristics of rheumatoid arthritis (RA) and cancer, particularly their unchecked growth and invasive behaviors, have been apparent for some time. (biomedcentral.com)
  • RT "Conjugation by ubiquitin-like proteins. (pdbj.org)
  • Conjugation of the Atg8 (autophagy related 8) family of ubiquitin-like proteins to phospholipids of the phagophore is a hallmark of macroautophagy/autophagy. (babraham.ac.uk)
  • Ligand binding induces the dimerization of receptor subunits marketing autophosphorylation from the receptor and recruiting a number of intracellular docking proteins (such as for example Grb2 Shc and Nck) towards the plasma membrane. (ecologicalsgardens.com)
  • Non-receptor protein tyrosine kinase which is activated following engagement of many different classes of cellular receptors including immune response receptors, integrins and other adhesion receptors, receptor protein tyrosine kinases, G protein-coupled receptors as well as cytokine receptors. (drugbank.com)
  • It consists of two domains: a G domain of 166 amino acids (about 20 kDa) that binds guanosine nucleotides, and a C-terminal membrane targeting region (CAAX-COOH, also known as CAAX box), which is lipid-modified by farnesyl transferase, RCE1, and ICMT. (wikipedia.org)
  • Ras also binds a magnesium ion which helps to coordinate nucleotide binding. (wikipedia.org)
  • We determined that CDC25 binds tightly to Ras2 protein only in the absence of guanine nucleotides. (cshl.edu)
  • However upon recruitment of Sos to the 4-Methylumbelliferone membrane Sos binds Ras-GDP and facilitates release of GDP. (ecologicalsgardens.com)
  • GTP binds to Ras by mass action. (ecologicalsgardens.com)
  • All Ras protein family members belong to a class of protein called small GTPase, and are involved in transmitting signals within cells (cellular signal transduction). (wikipedia.org)
  • Second this agent accelerates the internalization and degradation of HER-2 reducing the cellular level of activated tyrosine protein kinase. (ecologicalsgardens.com)
  • The flagpole is a conserved element in the RalGDS family of guanine nucleotide exchange factors and stabilises the orientation of the REM-domain relative to the CDC25-homology domain. (rcsb.org)
  • Structurally, the RA domain of RalGDS consists of a five-stranded mixed beta- sheet interrupted by a 12 residue alpha-helix and two additional small alpha- helices. (embl-heidelberg.de)
  • The major interaction between Ras and RalGDS RA domain occurs between two antiparallel beta-strands: beta 2 of Ras and beta 2 of RA. (embl-heidelberg.de)
  • One is the C-terminal Ras-associating domain bearing a structural homology with those of RalGDS and AF-6. (embl-heidelberg.de)
  • Arfs are ubiquitous in eukaryotes, are very highly conserved both structurally and functionally, and exchange guanine nucleotides in a complex, highly regulated fashion that is sensitive to lipids, salts, and divalent metals. (nih.gov)
  • 2014 ). The evolutionary conserved ubiquitin-proteasome system (UPS) and autophagy-lysosome pathway are the two major protein clearance mechanisms in eukaryotes. (springer.com)
  • Indeed, S(GDP) of Gα(t), is characterized by a more extensive energy coupling between nucleotide binding site and distal regions involved in GEF recognition compared to small G proteins, which attenuates in the active state. (irbbarcelona.org)
  • Now, a family of regulatory GTP-binding proteins has been observed to possess many of the features predicted for integrators of such interactions. (nih.gov)
  • Various regulatory proteins modulate the rate of conversion between these two states. (digglicious.com)
  • At the Drosophila neuromuscular junction (NMJ), the small GTPase Rab3 controls the distribution of CAZ proteins across release sites, thereby regulating the efficacy of individual AZs. (eneuro.org)
  • We show here that Rab3-GEF is required for controlling the protein composition of release sites in the Drosophila neuromuscular junction (NMJ). (eneuro.org)
  • The region required for full biological activity is approximately 450 residues and contains two segments homologous to other proteins: one found in both Ras-specific exchange factors and the more distant Bud5 and Lte1 proteins, and a smaller segment of 48 amino acids found only in the Ras-specific exchange factors. (cshl.edu)
  • A main feature of the catalytic domain is the protrusion of a helical hairpin important for the nucleotide-exchange mechanism. (embl.de)
  • This entry represents the catalytic domain of the Ras guanine-nucleotide exchange factors. (embl.de)
  • In COS-1 cells, the DH domain of Sos stimulated guanine nucleotide exchange on Rac but not Cdc42 in vitro and in vivo. (embl.de)
  • It is a guanine nucleotide exchange factor for RAS PROTEINS . (nih.gov)
  • Their study correlates expression of the Ras guanine nucleotide exchange factor RasGRF1 with MMP-3 expression in RA synovium. (biomedcentral.com)
  • Through mutational analysis we show that full nucleotide exchange activity requires a novel N-terminal extension on the DH domain that is predicted to exist in a broader family of RhoGEFs that includes p115-RhoGEF, Lbc, Lfc, Net1, and Xpln, and identify regions within the LARG PH domain that contribute to its ability to facilitate nucleotide exchange in vitro. (rcsb.org)
  • The protein contains approximately 188 amino acids with highly conserved residues 1-166 and with considerably variable C-terminal hypervariable region (HVR). (nih.gov)
  • Although the GTPase switch of Rab proteins is highly conserved, functional mechanisms may be highly diversified among members of the Rab family. (embl.de)
  • Bud5 from yeast, that may interact with the ras-like protein RSR1/BUD1. (embl.de)
  • RT "Interferon induces a 15-kilodalton protein exhibiting marked homology to RT ubiquitin. (pdbj.org)
  • The structure consists of two distinct alpha helical structural domains: the N-terminal domain which seems to have a purely structural role and the C-terminal domain which is sufficient for catalytic activity and contains all residues that interact with Ras. (embl.de)
  • We further modeled a full structure of K-Ras4B with the farnesylated HVR interacting with the lipid bilayer, suggesting the mechanisms of functional and conformational Ras On and Off states. (nih.gov)
  • To more directly study the physical interaction of CDC25 and Ras proteins, we developed a protein-protein binding assay. (cshl.edu)
  • This protein possesses both a domain belonging to the CDC25 family and one belonging to the CDC24 family. (embl.de)
  • RasGRF1 Cdc25 GEF protein domain from Cytoskeleton, Inc. (cytoskeleton.com)
  • The Cdc25 domain of human RasGRF1 protein has been produced in a bacterial expression system. (cytoskeleton.com)
  • Our results indicate that loss of Rab3-GEF results in the development of NMJs that are structurally and functionally indistinguishable from NMJs that lack the protein Rab3. (eneuro.org)
  • 1995), the interaction is via an inter-protein beta-sheet between the switch I region of Ras and the second strand of the RGS-RBD sheet, but the details of the interactions in the interface are remarkably different. (embl-heidelberg.de)
  • In this study we performed a comprehensive analysis of the relationship between the phylogeny of RAS proteins and their location in the protein interaction network. (oncotarget.com)
  • Unfortunately, many of the candidate therapeutic targets that have emerged from these advances have been deemed "undruggable" according to conventional definitions ( 1 ), and are frequently characterized by large protein-protein interaction surfaces that lack obvious ligandable pockets. (aacrjournals.org)
  • CR1 contains a Ras-binding domain (RBD), which is necessary for the interaction with Ras and with membrane phospholipids required for membrane recruitment, and a cysteine-rich domain (CRD), which is a secondary Ras-binding site and also necessary for the interaction of CR1 with the kinase domain for Raf auto-inhibition. (axonmedchem.com)
  • One reason this synthesis has not emerged is that we simply don't know how the cell "reads" and processes information inherent in the lipid composition of a membrane and integrates it into interactions with integral and peripheral membrane proteins. (nih.gov)
  • Ras is a membrane-associated guanine nucleotide-binding protein that is normally activated in response to the binding of extracellular signals through membrane receptors to intracellular signaling cascades. (nih.gov)
  • When cells adhere via focal adhesions to the extracellular matrix, signals are transmitted by integrins into the cell resulting in tyrosine phosphorylation of a number of focal adhesion proteins, including PTK2/FAK1 and paxillin (PXN). (drugbank.com)