Activity mutation ras gtpase activating proteins. Medical search. Frequent questions

NF1 codes for neurofibromin, a GTPase-activating protein that negatively regulates RAS/MAPK pathway activity by accelerating the hydrolysis of Ras-bound GTP. (wikipedia.org)
Neurofibromin, a GTPase-activating protein, primarily regulates the protein Ras. (wikipedia.org)
The presence or absence of 23a regulates Ras/ERK signalling and affects memory and learning behaviour 12 . (nature.com)
Neurofibromin, the protein product of the NF1 gene, functions at least in part as a GTPase activating protein that regulates Ras proteins by stimulating their intrinsic GTPase activity. (iu.edu)
4 In In NF1, this upregulation is caused by a germline pathogenic mutation on chromosome 17q11.2 in the NF1 tumor suppressor gene that codes for neurofibromin, a GTPase-activating protein (GAP) that negatively regulates RAS. (tamhsc.edu)
The heterodimeric TSC complex negatively regulates mTORC1 activity via the GTPase activity of TSC2, towards the small G-protein RHEB (Ras homologue enriched in brain) [ 5 ]. (springer.com)
Germline mutation results in Li-Fraumeni syndrome (2nd hit is somatic), characterized by the propensity to develop multiple types of carcinomas and sarcomas, C, Rb also regulates progression from G, to S phase. (ctsqena.com)
Rasip1 regulates activity of Rho GTPases in part by recruiting Briciclib the RhoA-specific GTPase activating protein (GAP) Arhgap29. (bioinbrief.com)
Seipel K, O'Brien SP, Iannotti E, Medley QG, Streuli M. Tara, a novel F-actin binding protein, associates with the Trio guanine nucleotide exchange factor and regulates actin cytoskeletal organization. (medecinesciences.org)

RHEB is a member of the small GTPase superfamily and encodes a lipid-anchored, cell membrane protein with five repeats of the RAS-related GTP-binding region. (signalchem.com)
Ras superfamily GTPase activation and inactivation occur by canonical nucleotide exchange and GTP hydrolysis mechanisms. (elifesciences.org)
The Rab subfamily of proteins is part of the large Ras superfamily, and all members of this superfamily are activated and inactivated in a similar way, with the binding and unbinding of GDP and GTP taking place at a structure called the G-domain. (elifesciences.org)
The GTPase superfamily: conserved structure and molecular mechanism. (xenbase.org)
Human RAS superfamily proteins and related GTPases. (xenbase.org)
Members of your Ras superfamily of little GTPases are widely deemed to be monomeric (23). (calcium-channel.com)
Rho GTPases are small (20-30 kDa) GTP-binding proteins of the Ras superfamily. (biomedcentral.com)

EVI2A and EVI2B are human homologs of the Evi-2A and Evi-2B genes in mice that encode proteins related to leukemia in mice. (wikipedia.org)
NF1 has one of the highest mutation rates amongst known human genes, however mutation detection is difficult because of its large size, the presence of pseudogenes, and the variety of possible mutations. (wikipedia.org)
Activating mutations in Ras genes are found in 33% of human cancers, with Ras well recognized as the most commonly mutated oncogene in human cancer. (aacrjournals.org)
Numerous studies have linked intellectual disability with mutations in genes coding for protein active at the synapses. (umontreal.ca)
Mutations in the tumor suppressor genes encoding TSC1 (Hamartin) and TSC2 (Tuberin) cause a multisystemic tumor syndrome termed tuberous sclerosis complex (TSC). (springer.com)
Mutations/deletions in separate genes, each of which alone causes a minimal phenotype, but when combined in the same cell results in a more severe fitness defect or lethality under a given condition. (thebiogrid.org)
RAB3GAP1 gene mutations are the most common cause of Warburg micro syndrome, although mutations in any of the genes can result in this condition. (medlineplus.gov)
The RAB3GAP1 , RAB3GAP2 , and TBC1D20 genes provide instructions for making proteins that regulate the activity of this protein. (medlineplus.gov)

The RAS-regulated RAF-MEK1/2-ERK1/2 signalling pathway is frequently de-regulated in human cancer. (babraham.ac.uk)
However, recent studies have suggested that BRAFi/MEKi and ERK1/2i resistance can arise through activation of a parallel signalling pathway leading to activation of ERK5, an unusual protein kinase that contains both a kinase domain and a transcriptional transactivation domain. (babraham.ac.uk)
Neurofibromatosis Type 1 (NF1) is an autosomal dominant genodermatotic and tumor predisposition disorder characterized by a mutation in the NF1 gene, a regulator of the RAS/MAPK pathway. (tamhsc.edu)
Studies indicate that the majority of pLGGs arise from a single genetic event leading to the upregulation of the RAS/MAPK pathway. (tamhsc.edu)
Current research shows that the inactivation of neurofibromin in patients with NF-1 leads to the overactivation of the Ras/MAPK pathway and increased incidence of pediatric low-grade gliomas and optic gliomas. (tamhsc.edu)
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)
Our results demonstrate an association between cognitive impairment and a defect in a signalling pathway that depends on a Ras-like GTPase. (embl-heidelberg.de)
Despite conservation of active-site residues, the Ras-related Rab GTPase activation pathway differs from Ras and between different Rabs. (elifesciences.org)
Furthermore, Rab1 switch II glutamine mutants refractory to activation by DrrA can be activated by TRAPP, showing that a single Rab can be activated by more than one mechanistically distinct GDP-release pathway. (elifesciences.org)
Chp, a homologue of the GTPase Cdc42Hs, activates the JNK pathway and is implicated in reorganizing the actin cytoskeleton. (xenbase.org)
Gauthier-Rouviere C, Vignal E, Meriane M, Roux P, Montcourier P, Fort P. RhoG GTPase controls a pathway that independently activates Rac1 and Cdc42Hs. (medecinesciences.org)
The Ras-Raf-MEK-ERK pathway plays a central role in tumorigenesis and is a target for anticancer therapy. (aging-us.com)
The successful strategy based on the activation of cell death in Ras-expressing cells is associated with the suppression of kinases involved in Ras pathway. (aging-us.com)
Our data show that suppression of MEK/ERK pathway in senescent cells provides a new strategy for elimination of Ras-expressing cells. (aging-us.com)
Despite a large number of promising inhibitors for Ras/Raf/MEK/ERK pathway, recent works show that cancer cells often develop an autophagy-dependent resistance to inhibitors of Ras pathway [ 16 ]. (aging-us.com)
Oncogenic Ras induces the constitutive activation of Ras/Raf/MEK/ERK signaling pathway, which, in turn, activates other effector pathways, in particular, PI3K-mTOR signaling [ 17 ]. (aging-us.com)

GTPase activator proteins towards Rho/Rac/Cdc42-like small GTPases. (embl-heidelberg.de)
Like all other GTPases, Rho proteins act as molecular switches, with an active GTP-bound form and an inactive GDP-bound form. (embl-heidelberg.de)
2007), Evolution of the Rho family of ras-like GTPases. (xenbase.org)
On the other hand, a number of members across the Ras GTPase subfamilies are now identified to dimerize (248), plus a class of tiny GTPases that use dimerization rather than GTPase activating proteins (GAPs) for GTPase activity has been identified (29). (calcium-channel.com)
Rem2 is a member of the RGK family of small Ras-like GTPases whose expression and function is regulated by neuronal activity in the brain. (health-ground.com)
Introduction The RGK (Ras, Rem, Rem2, Gem/Kir) protein family is a subclass of small Ras-like GTPases structurally distinct from canonical GTPases. (health-ground.com)
Although dozens of proteins act downstream of these GTPases, a comparison of effector proteins from evolutionarily diverse organisms suggests that six groups of proteins serve as the core machinery for signaling from Cdc42 and Rac. (biomedcentral.com)
Interestingly, small GTPases related to Rac are found even in organisms that lack Ras, such as plants. (biomedcentral.com)
This broad distribution across widely divergent eukaryotic species suggests that Cdc42 and Rac GTPases have an ancient origin, perhaps even predating that of their cousin Ras. (biomedcentral.com)
The DH protein family, exchange factors for Rho-like GTPases. (medecinesciences.org)

A scaffold protein DAB2 and its interaction partner DAB2IP have putative tumor suppressor gene (TSG) functions. (nih.gov)
The autosomal dominant monogenetic disease neurofibromatosis type 1 (NF1) affects approximately one in 3,000 individuals and is caused by mutations in the NF1 tumour suppressor gene, leading to dysfunction in the protein neurofibromin (Nf1) 1 , 2 . (nature.com)
Structure of the Ki-ras gene of the human lung carcinoma cell line Calu-1. (wikidata.org)
Mutations and gene amplifications that confer drug resistance emerge frequently during chemotherapy, but their mechanism and timing are poorly understood. (babraham.ac.uk)
De novo mutations in the SYNGAP1 gene, coding for a GTPase-activating protein, causes moderate to severe intellectual disability. (umontreal.ca)
Oncogenic RAS expression increased S100A10 gene expression which resulted in an increase in S100A10 protein levels. (oncotarget.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)
Mutations of the NF1 gene potentially results in the activation of multiple Ras proteins, which are key regulators of many biologic effects. (biomedcentral.com)
The GTPase signalling molecules RhoA and Rac1 regulate merlin function, but to date only mutation in the NF2 gene has been identified as a causal event in schwannoma formation. (bmj.com)
In 1986, the NF2 gene was mapped to chromosome 22, and in 1993, two groups independently isolated the gene and named its encoding protein merlin or schwannomin. (bmj.com)
5, 6 The NF2 gene is a tumour suppressor, as corroborated by studies showing complete inactivation of the gene in more than 60% of schwannomas, either by mutation in both alleles or by loss of one allele and mutation in the other. (bmj.com)
Here we report the characterization of a new gene on the long arm of the X-chromosome (position Xq12) and the identification in unrelated individuals of different mutations that are predicted to cause a loss of function. (embl-heidelberg.de)
This gene is highly expressed in fetal brain and encodes a protein of relative molecular mass 91K, named oligophrenin-1, which contains a domain typical of a Rho-GTPase-activating protein (rhoGAP). (embl-heidelberg.de)
Mutations in this gene have been associated with somatic rectal cancer, follicular thyroid cancer, autoimmune lymphoproliferative syndrome, Noonan syndrome, and juvenile myelomonocytic leukemia. (nih.gov)
Description of the protein which includes the UniProt Function and the NCBI Gene Summary. (nih.gov)
X-linked agammaglobulinemia (XLA) is an immunodeficiency caused by mutations in the gene coding for Bruton's tyrosine kinase (BTK) [Väliaho et al. (lu.se)
The gene affected encodes a SH2D1A protein consisting only of a SH2 domain and a short C-terminal tail [Sayos et al. (lu.se)
ZAP-70 deficiency is a rare autosomal recessive form of severe combined immunodeficiency (SCID) caused by mutations in the gene coding for T cell receptor z-chain associated protein kinase [ Chan et al. (lu.se)
Noonan syndrome (NS) is caused by mutations in PTPN11 , a gene encoding the nonreceptor protein tyrosine phosphatase SHP2. (lu.se)
Mutations in the PIK3R1 gene encoding phosphatidylinositol 3-kinase (PI3-kinase) have been found to cause severe insulin resistance [Baynes et al. (lu.se)
1997]. Mutations in the STAT1 gene cause complete STAT1 deficiency. (lu.se)
Point mutations in the Drosophila RHEB gene inhibits cell growth while overexpression promotes cell growth. (signalchem.com)
Genomic structure and assignment of the RhoH/TTF small GTPase gene (ARHH) to 4p13 by in situ hybridization. (xenbase.org)
these proteins are also important in regulating gene transcription. (biomedcentral.com)
In addition, they play important roles in gene transcription (via activation of mitogen activated protein (MAP) kinase pathways and, in higher eukaryotes, the transcription factor NFκB), generation of reactive oxygen species, apoptosis, and cell-cycle progression. (biomedcentral.com)
RAB18 deficiency is caused by mutations in the RAB3GAP1 , RAB3GAP2 , RAB18 , or TBC1D20 gene. (medlineplus.gov)
Mutations that cause Warburg micro syndrome completely eliminate the production or function of the protein produced from the gene. (medlineplus.gov)
Martsolf syndrome is caused by mutations in the RAB3GAP2 gene or rarely the RAB3GAP1 gene. (medlineplus.gov)
The RAB18 gene provides instructions for making the RAB18 protein. (medlineplus.gov)

Oncogenic mutations result in functional activation of Ras family proteins by impairing GTP hydrolysis. (rcsb.org)
RASA1 acts by enhancing the intrinsic GTPase activity of Ras, leading to hydrolysis of bound GTP to GDP and down regulation of Ras activity [Gold, et al. (lu.se)
The GAP of ARD1 stimulates GTPase hydrolysis for ARD1 but not ARFs. (embl.de)
Using ARD1 truncations, it appears that amino acids 101-190 are critical for GAP activity, whereas residues 190-333 are involved in physical interaction between the two domains of ARD1 and are required for GTP hydrolysis. (embl.de)

The active conformation is promoted by guanine-nucleotide exchange factors, and the inactive state by GTPase-activating proteins (GAPs) which stimulate the intrinsic GTPase activity of small G proteins. (embl-heidelberg.de)
Ras proteins bind GDP/GTP and possess intrinsic GTPase activity. (nih.gov)
The encoded protein, which has intrinsic GTPase activity, is activated by a guanine nucleotide-exchange factor and inactivated by a GTPase activating protein. (nih.gov)
The p53 interacting partner protein NUMB (homology of numb protein) preserves this intrinsic cellular asymmetry by preventing ubiquitin-mediated proteolysis of p53 catalyzed by the MDM2 E3 ubiquitin ligase 11 . (nature.com)

Putative zinc fingers with GTPase activating proteins (GAPs) towards the small GTPase, Arf. (embl.de)
Both guanine nucleotide-exchange proteins and GTPase-activating proteins (GAPs) for ARFs have been cloned recently. (embl.de)
Other proteins-known as GAPs-lead to the inactivation of the Rab protein. (elifesciences.org)
The major distinguishing features of the RGK protein family include: calmodulin and 14-3-3 protein binding sites, noncanonical amino acid substitutions in the guanine nucleotide binding domain, and a lack of identified guanine nucleotide exchange factors (GEFs) or GTPase activating proteins (GAPs) buy Decitabine [1]. (health-ground.com)

Proximal NF1 promoter/5' UTR methylation has been analyzed in tissues from NF1 patients, with the idea that reduced transcription as a result of methylation could be a "second hit" mechanism equivalent to a somatic mutation. (wikipedia.org)
Somatic Nf1 mutations are also present in 5-10% of cancers, demonstrating the role of Nf1 as a tumour suppressor 1 . (nature.com)
Somatic mutations in the small GTPase K-Ras are the most common activating lesions found in human cancer, and are generally associated with poor response to standard therapies. (rcsb.org)
Somatic mutations at the phosphotyrosine-binding pocket of the C-terminal SH2 domain of GTPase-activating protein RASA1 have been found in a subset of Basal-cell carcinoma (BCC) [Friedman, 1995]. (lu.se)
1999 ]. Germline mutations in PTPN11 lead to Noonan syndrome associated with JMML, and somatic PTPN11 mutations are associated with isolated JMML [Tartaglia et al. (lu.se)
Sporadic mutation (both hits are somatic) is characterized by unilateral retinoblastoma (Fig. 3,1). (ctsqena.com)
ii, Germline mutation results in familial retinoblastoma (2nd hit is somatic), characterized by bilateral retinoblastoma and osteosarcoma. (ctsqena.com)

The link between oncogenic RAS expression and the acquisition of the invasive phenotype has been attributed to alterations in cellular activities that control degradation of the extracellular matrix. (oncotarget.com)
Oncogenic RAS-mediated upregulation of matrix metalloproteinase 2 (MMP-2), MMP-9 and urokinase-type plasminogen activator (uPA) is critical for invasion through the basement membrane and extracellular matrix. (oncotarget.com)
These results strongly suggest that increases in cell surface levels of S100A10, by oncogenic RAS, plays a critical role in RAS-stimulated plasmin generation, and subsequently, in the invasiveness of oncogenic RAS expressing cancer cells. (oncotarget.com)

2,4 Thus, neurofibromin normally acts as a GAP, inhibiting Ras/MAPK signaling. (tamhsc.edu)
Loss of the Ras GTPase-activating protein neurofibromin promotes nervous system tumor pathogenesis in patients with neurofibromatosis type 1 (NF1). (biomedcentral.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)
Both proteins were activated in neurofibromin-null MPNST cells. (biomedcentral.com)
loss of neurofibromin could cause these Ras proteins to become persistently active, leading to the development of cancer. (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)
Here, we examined the expression, activation and action of R-Ras proteins in MPNST cells that have lost neurofibromin. (biomedcentral.com)

Consequently, mutated Nf1 shows altered Ras-GAP activity and leads to uncontrolled signalling in multiple cell signalling pathways. (nature.com)
Ras proteins are critical regulators of multiple pathways involved in cellular growth control. (aacrjournals.org)
Although data are relatively limited, studies have investigated the mechanisms of the disease progression in this patient population and found that pharmacological inhibition of the Ras/MAPK and/or mTOR signaling pathways are potential treatment options for NF1-pLGGs and optic gliomas. (tamhsc.edu)
Bioinformatics analysis showed that Complement and coagulation cascades and Platelet activation in immune-related pathways were significantly enriched, suggesting that differentially modified proteins among them may affect SLE. (bvsalud.org)
Khib modification of key proteins in the Complement and coagulation cascades and Platelet activation pathways affects platelet activation and aggregation, coagulation functions in SLE patients. (bvsalud.org)
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 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)
a variety of upstream signaling pathways can activate Ras-GDP to Ras-GTP, which subsequently selects amongst a number of downstream effectors to elicit a varied but distinct biochemical response (2, 3). (calcium-channel.com)
TBC1D15 activated three novel oncogenic pathways to promote self-renewal, p53 loss, and Nanog transcription in TICs. (nature.com)

Right here, we propose a molecular system where AJC scaffolding proteins control apical cell contractility by differentially recruiting MAGI-1 and MAGI-3 to apical AZD-3965 junctions. (aboutsciencenow.info)
Molecular characterization of the GTPase-activating domain of ADP-ribosylation factor domain protein 1 (ARD1). (embl.de)
Basic sequence-derived (length, molecular weight, isoelectric point) and experimentally-determined (median abundance, median absolute deviation) protein information. (yeastgenome.org)
Together these proteins form a molecular switch that can be turned on and off. (elifesciences.org)
Lately, semisynthetic natively lipidated N-Ras was shown to cluster on supported membranes in vitro, inside a manner broadly consistent with molecular mechanics (MM) modeling of dimers (30). (calcium-channel.com)

This has led to the development of a range of ERK1/2 inhibitors (ERKi) that either inhibit kinase catalytic activity (catERKi) or additionally prevent the activating pT-E-pY dual phosphorylation of ERK1/2 by MEK1/2 (dual-mechanism or dmERKi). (babraham.ac.uk)
They also activate other kinase cascades. (embl-heidelberg.de)
Active mTORC1 phosphorylates the eukaryotic initiation factor 4E-binding protein-1 (4E-BP1) and 40S ribosomal protein S6 kinase 1 (S6K1) to promote protein synthesis [ 3 , 4 ]. (springer.com)
Conversely, during starvation mTORC1 is inhibited and autophagy is induced by AMP-activated protein kinase (AMPK), leading to generation of intracellular nutrients and energy during degradation of non-functional or non-essential organelles or protein aggregates [ 4 , 6 ], in turn contributing to cell survival. (springer.com)
The multidomain protein Trio binds the LAR transmembrane tyrosine phosphatase, contains a protein kinase domain, and has separate rac- specific and rho-specific guanine nucleotide exchange factor domains. (medecinesciences.org)

7 Moreover, germline NF1 mutations differentially increase proliferation of progenitor cells during embryogenesis. (tamhsc.edu)
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)
Additionally, RGK proteins are differentially expressed in specific tissues with transcriptional regulation of their mRNA manifestation mediated by way of a selection of extrinsic elements (i.e. blood sugar, mitogens, and neuronal depolarization) [1,11C14]. (health-ground.com)

It has recently been shown that K-Ras monoubiquitination, upregulates its activity by populating the active GTP-bound state, enhances interactions with certain downstream effectors and promotes Ras-mediated tumorigenesis [1]. (aacrjournals.org)
This gives GTP an advantage over GDP and increases the proportion of active GTP-bound Ras. (rcsb.org)
Mutations to codon 12 in KRAS maintains kRAS in an active, GTP-bound state through preventing GTPase-activating proteins (GAP) association. (cytoskeleton.com)

The NF1 locus has a high incidence of de novo mutations, meaning that the mutations are not inherited maternally or paternally. (wikipedia.org)
About half of all cases of NF1 are inherited, whereas the remaining cases result from de novo mutations 10 . (nature.com)

Small GTPase Tc10 and its homologue RhoT induce N-WASP-mediated long process formation and neurite outgrowth. (xenbase.org)

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)
The 70 or so members of the Rab subfamily of proteins perform a wide range of important tasks inside cells. (elifesciences.org)

We will also present our recent work on an oncogenic variant prevalent in lung cancer, K-Ras G12C. (aacrjournals.org)
We find that this activating mutation introduces a redox active cysteine that renders Ras G12C sensitive to thiol oxidation. (aacrjournals.org)
Here we report the development of small molecules that irreversibly bind to a common oncogenic mutant, K-Ras(G12C). (rcsb.org)
Binding of these inhibitors to K-Ras(G12C) disrupts both switch-I and switch-II, subverting the native nucleotide preference to favour GDP over GTP and impairing binding to Raf. (rcsb.org)
Common mutations include G12C, G12D, G12V which account for nearly 80% of all KRAS mutations. (cytoskeleton.com)
Recently, a drug that targets mutant RAS G12C specifically has shown promising clinical results and is now the first FDA approved RAS-targeting drug for the treatment of NSCLC, read on for a summary of this drugs journey from discovery to approval, and roadblocks that still lie ahead. (cytoskeleton.com)

SPRED1 recruits Nf1 from the cytosol to the plasma membrane where Ras resides, and Nf1 subsequently can downregulate GTP-bound Ras 14 . (nature.com)
Members of the Rho family of small G proteins transduce signals from plasma-membrane receptors and control cell adhesion, motility and shape by actin cytoskeleton formation. (embl-heidelberg.de)
This is an N-ras oncogene encoding a membrane protein that shuttles between the Golgi apparatus and the plasma membrane. (nih.gov)
Isoform-specific posttranslational lipidation targets the key H-, N-, and K-Ras isoforms to diverse subdomains of the plasma membrane (80). (calcium-channel.com)
Nevertheless, whether VGCC inhibition is because of interference with route trafficking towards the plasma membrane by RGK protein [21] or RGK-mediated inactivation of stations already at the top [8,16], continues to be questionable. (health-ground.com)

By enhancing their GTPase activity, GAP proteins inactivate small Rho and Ras proteins, so inactivation of rhoGAP proteins might cause constitutive activation of their GTPase targets. (embl-heidelberg.de)
EGFR downstream signaling promotes constitutive activation of TKIs domain due to the mutation in exon 19 and exon 21 (L858R point mutation), which leads to cell proliferation, invasion, metastasis, and angiogenesis, causing lung adenocarcinoma. (lidsen.com)

These findings represent a paradigm shift in our understanding of the role monoubiquitination may play in protein regulation as well as new mechanisms for regulation of Ras activity. (aacrjournals.org)
3. Differences in the regulation of k-ras and h-ras isoforms by monoubiquitination.Baker R, Wilkerson EM, Sumita K, Isom DG, Sasaki AT, Dohlman HG, Campbell SL.J Biol Chem. (aacrjournals.org)
With diminished regulation by GTPase activity, the nucleotide state of Ras becomes more dependent on relative nucleotide affinity and concentration. (rcsb.org)
Similarly, primary cilia have been implicated in regulation of mTOR signaling, in which Tuberous Sclerosis Complex proteins 1 and 2 (TSC1/2) negatively regulate protein synthesis by inactivating the mTOR complex 1 (mTORC1) at energy limiting states. (springer.com)

Consistent with classical Ras inhibition, DN R-Ras and R-Ras2 knockdown inhibited proliferation. (biomedcentral.com)
However, DN R-Ras inhibition impaired migration and invasion but not survival. (biomedcentral.com)
Inhibition of R-Ras action inhibited proliferation, migration and invasion but not survival. (biomedcentral.com)
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)
RGK proteins have been implicated in mediating cytoskeletal rearrangements [2C5] and inhibition of voltage-gated calcium channel currents [6C10]. (health-ground.com)
We studied whether cellular senescence induced by HDAC inhibitor sodium butyrate in E1a+cHa-Ras -transformed rat embryo fibroblasts (ERas) and A549 human Ki-Ras mutated lung adenocarcinoma cells would enhance the tumor suppressor effect of MEK/ERK inhibition. (aging-us.com)

During starvation AMPK promotes autophagy by activating ULK1 via phosphorylation at Ser317, Ser555, and Ser777, whereas in the presence of nutrients mTORC1 suppresses autophagy by hampering interaction between AMPK and ULK1 through phosphorylation of ULK1 at Ser757 [ 7 ]. (springer.com)
Significantly, the mutation of crucial phosphorylation sites within the Rem2 coding series inhibits Rem2 nuclear localization and causes improved dendritic difficulty, buy Decitabine mimicking the Rem2 RNAi phenotype and additional supporting the role of Rem2 as a negative regulator of dendritic complexity [24]. (health-ground.com)

Both DAB2 and DAB2IP have mononucleotide repeats in their coding sequence that could be mutation targets in high microsatellite instability (MSI-H) cancers. (nih.gov)
DAB2 frameshift mutations were found in 2 of 79 CRCs (2.5%) with MSI-H. These mutations were not detected in microsatellite stable (MSS) cancers. (nih.gov)
Soluble Ras doesn't activate Raf SignificanceRas is usually a key signaling molecule in living cells, and mutations in Ras are involved in 30 of human cancers. (calcium-channel.com)
Although TICs are identified in different types of cancers and represent a hallmark of therapy-resistance 3 , there is no coherent understanding of the underlying mechanisms for their unchecked proliferation, tumorigenic activity, and clinical intractability. (nature.com)
Ras GTPase is frequently mutated in different types of cancers that correlate with a poor prognosis [ 11 - 15 ]. (aging-us.com)

In this function, we use a series of quantitative physical methods to map out the tendency of two Ras molecules to bind with each other to type a dimer on membrane surfaces. (calcium-channel.com)

Melanoma in particular exhibits a high incidence of activating BRAF and NRAS mutations and such cells are addicted to the activity of these mutant oncoproteins. (babraham.ac.uk)
2003]. The disorder can also be caused by mutations in NRAS , KRAS2 , NF1 , or GRAF . (lu.se)

These compounds rely on the mutant cysteine for binding and therefore do not affect the wild-type protein. (rcsb.org)
Our data provide structure-based validation of a new allosteric regulatory site on Ras that is targetable in a mutant-specific manner. (rcsb.org)
Although the RAS family of proteins was discovered nearly four decades ago there has not been a viable drug therapy developed to effectively blocks mutant RAS dysfunction. (cytoskeleton.com)
Therefore, autophagy is currently considered as a promising target for anticancer therapy that can also be successful in mutant Ras-expressing tumors characterized by chemotherapy resistance due to the protective autophagy. (aging-us.com)

In this scholarly study, we present proof that MAGI proteins, structural the different parts of AJC whose function continued to be unclear, regulate apical constriction of epithelial cells through the Par polarity proteins. (aboutsciencenow.info)
In this review we will highlight mechanisms that control targeting of PSD-95 at the synapse, and discuss how this molecule influences the retention and clustering of diverse synaptic proteins to regulate synaptic structure and strength. (frontiersin.org)
Trio combines with dock to regulate Pak activity during photoreceptor axon pathfinding in Drosophila. (medecinesciences.org)

We analyzed GC and CRC tissues and found that 8 of 34 GCs (23.5%) and 15 of 79 CRCs (20.0%) with MSI-H harbored DAB2IP frameshift mutations. (nih.gov)
Our study shows that the TSG DAB2IP harbored frameshift mutations and ITH as well as expression loss. (nih.gov)
For example, patients with nonsense or frameshift mutations generally have severe disease, whereas missense mutations usually cause mild disease. (bmj.com)

We have shown that classic Ras proteins promote proliferation and survival, but not migration, in malignant peripheral nerve sheath tumor (MPNST) cells. (biomedcentral.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)
Freely available on the internet by way of the PNAS open access option.1In mammalian signal transduction, Ras functions as a binary switch in fundamental processes like proliferation, differentiation, and survival (1). (calcium-channel.com)

Crystallographic studies reveal the formation of a new pocket that is not apparent in previous structures of Ras, beneath the effector binding switch-II region. (rcsb.org)

Depletion of S100A10 from RAS-transformed cells resulted in a loss of both cellular plasmin generation and invasiveness. (oncotarget.com)
Results Lack of ZO proteins highly perturbs Par-3 localization and alters apical morphology We previously demonstrated that depletion of ZO proteins in the mouse mammary epithelial cell range, EpH4, delays the forming of the contractile belt-like AJ18, recommending that ZO proteins are necessary for epithelial polarization. (aboutsciencenow.info)

While polyubiquitination of proteins leads to protein degradation, reversible covalent modification by monoubiquitination can lead to alterations in trafficking and subcellular localization. (aacrjournals.org)
Notably, loss of SMAD specific E3 ubiquitin protein ligase 2 abolishes the ubiquitination and degradation of SMAD2 induced by SIRT2 in SMAD2. (bvsalud.org)
Cell-fate-determinant molecule NUMB-interacting protein (TBC1D15) is overexpressed and contributes to p53 degradation in TICs. (nature.com)
Autophagy represents a caspase-independent process characterized by accumulation of autophagosomes in the cytoplasm and their subsequent fusion with lysosomes for degradation of unused or misfolded proteins or damaged structures such as ribosomes (ribophagy) and mitochondria (mitophagy). (aging-us.com)

Point mutations are the most usual constitutional NF2 mutations in NF2 patients, whereas small deletions are the main causal event in unilateral sporadic vestibular schwannoma. (bmj.com)

Mutations in Ras associated with cancer promote cellular activation by populating the active state of Ras, most frequently by impairing the action of proteins that downregulate its activity. (aacrjournals.org)
We have investigated novel mechanisms of Ras activation by posttranslational modification. (aacrjournals.org)
1. Ubiquitination of K-Ras enhances activation and facilitates binding to select downstream effectors. (aacrjournals.org)
ADP-ribosylation factors (ARFs) are approximately 20-kDa guanine nucleotide-binding proteins recognized as critical components in intracellular vesicular transport and phospholipase D activation. (embl.de)
The experiments showed that different amino acids in the active site of the Rab protein are involved when the GEFs mediate the release of the GDP during the activation process. (elifesciences.org)
For example, the amino acid glutamine is involved when the Listeria GEF and one of the human GEFs activate the protein, whereas a different amino acid-aspartate-is involved when one of the other human GEFs is responsible for the activation. (elifesciences.org)
For Ras, dimerization could possibly be significant since Raf, that is recruited to the membrane by binding to Ras, calls for dimerization for activation. (calcium-channel.com)

Therefore, we exposed the MAGIs are crucial regulators of Par polarity proteins that are central towards the rules of pressure distribution in epithelial cells homeostasis. (aboutsciencenow.info)

Ras signaling can be thought of in simple terms as occuring downstream of receptor tyrosine kinases, triggered by association of adaptor proteins with the phosphorylated cytoplasmic tails of these receptors. (sdbonline.org)
This motif is found in Cdc42/Rac-associated proteins such as the protein kinases Pak, MRCK and Ack, the adaptor proteins Spec and WASP, and, in degenerate form, in the kinases MLK, Mekk4, adaptor Par6, scaffold protein IRSp53, and the Borg proteins. (biomedcentral.com)

1998], and mutations in the STAT5B SH2 domain in humans lead to growth hormone insensitivity with immunodeficiency [Kofoed et al. (lu.se)

Guanosine nucleotide binding by highly purified Ha-ras-encoded p21 protein produced in Escherichia coli. (wikidata.org)
Proteins called guanine nucleotide exchange factors, or GEFs for short, activate the Rab protein by promoting the release of GDP and the binding of GTP. (elifesciences.org)

In the presence of nutrients, mTORC1 is activated and promotes cell growth, including protein synthesis and energy storage. (springer.com)
For example, the cvclinD/CDK4 complex phosphorylates the retinoblastoma protein, which promotes progression through the G^S checkpoint. (ctsqena.com)

Five regions of the 3' UTR that appear to bind proteins were found, one of which is HuR, a tumor antigen. (wikipedia.org)
In mammalian cells, as many as twenty types of protein have been reported to bind to activated Cdc42 [ 2 ]. (biomedcentral.com)

The Gap1 catalytic domain alone is insufficient for in vivo activity of Gap1, indicating a requirement for the additional domains. (sdbonline.org)
An inositol-1,3,4,5-tetrakisphosphate (IP4)-sensitive extended PH domain is essential for Gap1 activity, while Ca2+-sensitive C2 domains and a glutamine-rich region contribute equally to full activity in vivo. (sdbonline.org)
Drosophila RHEB is a direct target of Tsc2 GTPase-activating protein (GAP) activity both in vivo and in vitro. (signalchem.com)
STAT3 Purity & Documentation Whereas these allosteric modes likely contribute to Ras partitioning and reorientation in vivo, direct functional consequences on Ras protein rotein interactions are poorly understood. (calcium-channel.com)

As a GTPase-activating protein, a key function of Nf1 is repression of the Ras oncogene signalling cascade. (nature.com)
2. Site-Specific Monoubiquitination Activates Ras by Impeding GTPase Activating Protein Function. (aacrjournals.org)
The site abundance, distribution and function of Khib protein were investigated further. (bvsalud.org)
MAGIs further localize a range of scaffolding and signaling proteins that recruit and control Par-3 function to modulate contractility from the AJC-linked actomyosin network. (aboutsciencenow.info)
It really is becoming progressively extra clear that the spatial arrangement of proteins within a cell, not just their chemical structure, is an critical aspect of their function. (calcium-channel.com)
The analysis of Cdc42 and Rac function in evolutionarily distant organisms is useful as a tool to uncover the basic activities of these proteins. (biomedcentral.com)
This activity is strongly conserved and probably represents a primordial function of these proteins. (biomedcentral.com)
Mutations that result in Martsolf syndrome reduce but do not eliminate protein function. (medlineplus.gov)

Ras is associated with growth factor receptors in an inactive GDP-bound state. (ctsqena.com)
A Rab protein is always bound to another molecule, which determines whether it is inactive or active. (elifesciences.org)
Binding to a molecule called GDP makes the Rab protein inactive, while binding to GTP makes it active. (elifesciences.org)

5,6 In cancer predisposition syndromes such as NF1, the role of neuronal activity in tumor progression is relatively unknown, with limited available data. (tamhsc.edu)
B. DNA mutations eventually disrupt key regulatory systems, allowing for tumor promotion (growth) and progression (spread). (ctsqena.com)
Rb mutation results in const it utively free E2F, allowing progression through the cell cycle and uncontrolled growth of cells. (ctsqena.com)

NF1 has a high mutation rate and mutations in NF1 can alter cellular growth control, and neural development, resulting in neurofibromatosis type 1 (NF1, also known as von Recklinghausen syndrome). (wikipedia.org)

RHEB has GTPase activity and shuttles between a GDP-bound form and a GTP-bound form. (signalchem.com)
2. Zhang, Y. et al: Rheb is a direct target of the tuberous sclerosis tumour suppressor proteins. (signalchem.com)

The phosphorylated form of 40S ribosome protein S6 is thus a marker for mTORC1 activity. (springer.com)
Given that autophagy is initiated upon suppressed mTORC1 activity, a protective autophagy in Ras-transformed cells with a high level of mTORC1 activity appears to be mTORC1-independent [ 20 , 21 ]. (aging-us.com)

To determine the mechanism by which ubiquitination activates Ras, we conducted NMR, modeling, biochemical and biological studies of monoubiquitinated H-Ras and K-Ras. (aacrjournals.org)
By showing that different Rab proteins are activated by different mechanisms, and that a single Rab protein can be activated by more than one mechanism, the work of Langemeyer et al. (elifesciences.org)
Further NOD1 Formulation modeling showed that the membrane binding region and the canonical switch I and II regions communicate across the protein by means of long-range side-chain interactions (21) in a conformational choice mechanism (22). (calcium-channel.com)

Oligophrenin-1 encodes a rhoGAP protein involved in X-linked mental retardation. (embl-heidelberg.de)

this is augmented by GTPase activating protein, v. Mutated ras inhibits the activity of GTPase activating protein. (ctsqena.com)

Signaling specificity is achieved by a combination of conformational plasticity in Ras itself (4, 5) and dynamic manage of Ras spatial organization (six, 7). (calcium-channel.com)

Residues conserved across the rhoGAP family are largely confined to one face of this bundle, which may be an interaction site for target G proteins. (embl-heidelberg.de)

Mutations in NF1 cause the common genetic disorder neurofibromatosis type 1 (NF1) which is associated with a predisposition to neural crest derived tumors and juvenile myelomonocytic leukemia (JMML). (iu.edu)
Validation of R-Ras and R-Ras2 action and R-Ras regulated networks was performed using genetic and/or pharmacologic approaches. (biomedcentral.com)

Anatomy17

Organisms12

Diseases7

Chemicals and Drugs98

Analytical, Diagnostic and Therapeutic Techniques and Equipment26

Phenomena and Processes94

Disciplines and Occupations1

Information Science4

Named Groups1

Health Care4

Regulates9

Superfamily7

Genes8

Pathway16

GTPases10

Gene29

Hydrolysis4

Intrinsic4

GAPs4

Somatic7

Oncogenic ras3

Neurofibromin7

Pathways9

Molecular5

Kinase5

Differentially3

Active GTP-bound3

Novo mutations2

Homologue1

Subfamily2

G12C6

Plasma membrane5

Constitutive2

Regulation4

Inhibition6

Phosphorylation2

Cancers5

Molecules1

NRAS2

Mutant4

Regulate3

Frameshift mutations3

Proliferation3

Effector1

Depletion2

Degradation4

Point mutations1

Activation7

Regulators1

Adaptor proteins2

19981

Nucleotide2

Promotes2

Bind2

Vivo4

Function8

Inactive3

Progression3

Cellular growth control1

RHEB2

MTORC1 activity2

Mechanism3

Encodes1

Inhibits1

Plasticity1

Residues1

Genetic2