• 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)
  • Manzerra, Pasquale, Synaptic Ras GTPase activating protein (SynGAP) regulates N-methyl-D-aspartate receptor (NMDAR)-mediated excitotoxicity via P38 MAPK activation. (usd.edu)
  • In addition, cAMP binds to and regulates the function of ion channels such as the HCN channels and a few other cyclic nucleotide-binding proteins such as Epac1 and RAPGEF2 . (wikipedia.org)
  • 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)
  • SynGAP(Synaptic Ras GTPase-activating protein) is a protein that regulates function in synapses. (purdue.edu)
  • Acts as a 'third messenger' substrate of protein kinase C-mediated molecular cascades during synaptic development and remodeling. (embl.de)
  • 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)
  • In this manner the neurons strike a "balance" that allows for neurons to become activated and convey discrete synaptic signals, while preventing excessive excitation. (frontiersin.org)
  • These proteins aggregate at presynaptic active zones (AZs) to form the cytomatrix at the active zone (CAZ), which controls the recruitment, docking, and priming of synaptic vesicles and enhances calcium channel accumulation ( Gundelfinger and Fejtova, 2012 ). (eneuro.org)
  • In addition, SynGAP protein is an integral component of the post-synaptic density and its role in signaling pathway converges with other autism risk genes and consequently autism risk proteins. (purdue.edu)
  • A scaffold protein DAB2 and its interaction partner DAB2IP have putative tumor suppressor gene (TSG) functions. (nih.gov)
  • Meanwhile, the DOC-2/DAB2 interacting protein DAB2IP was previously identified as a member of the Ras-GTPase activating protein family, and functions as a tumor suppressor in cancer progression 7 , 8 . (nature.com)
  • A Ras GTPase activating protein tumor suppressor, DAB2 interacting protein ( DAB2IP ), was discovered as an miR431 target. (quanterix.com)
  • DAB2IP is a Ras (MIM 190020) GTPase-activating protein (GAP) that acts as a tumor suppressor. (antikoerper-online.de)
  • The tuberous sclerosis protein (TSC) complex acts as a relay for anabolic signaling and as a tumor suppressor. (tugraz.at)
  • 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)
  • The pseudophosphatase MK-STYX (mitogen-activated protein kinase phosphoserine/threonine/tyrosine-binding protein) has been implicated in the stress response pathway. (wm.edu)
  • Results of their new study suggest that these malformations are a result of KRAS -induced activation of the mitogen-activated protein kinase-extracellular signal-regulated kinase (MAPK-ERK) signaling pathway in brain endothelial cells. (medscape.com)
  • Loss of DAB2IP protein expression was found in approximately 20% of GCs and CRCs irrespective of MSI and DAB2IP frameshift mutation status. (nih.gov)
  • In this study, we demonstrated that the loss of DOC-2/DAB2 interacting protein (DAB2IP) is responsible for TMZ-resistance in GBM through ATG9B. (nature.com)
  • Taken together, miR431 silences DAB2IP to active Ras/Erk and promote metastasis of PNETs. (quanterix.com)
  • The DOC-2/DAB2 interactive protein (DAB2IP) is a new member of the Ras GTPase-activating protein family. (elsevierpure.com)
  • These are termed Exchange proteins activated by cAMP (Epac) and the family comprises Epac1 and Epac2 . (wikipedia.org)
  • 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)
  • Mutations that produce abnormally active Ras proteins are common in human cancers, particularly those of the pancreas, lung, and colon. (cshlpress.com)
  • The contributors review the biochemical characteristics of the different Ras isoforms (HRAS, KRAS, and NRAS), their main effectors and signaling pathways, and the mutations that lead to their constitutive activation. (cshlpress.com)
  • In collaboration with a group at the University of Geneva (Dr S.I. Nikolaev and Dr S.E. Antonarakis) and the group of Dr J.E. Fish from University of Toronto, they performed exome DNA sequencing of the tissue samples of 26 patients and found somatic activating KRAS mutations in some of them. (medscape.com)
  • In total, the researchers detected somatic activating KRAS mutations in tissue samples from 45 of 72 patients and in none of the 21 paired blood samples. (medscape.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)
  • PKC phosphorylation of these proteins also inhibits their binding to RNA in vitro. (embl.de)
  • Overexpression of DAB2IP's rat homolog DIP, but not its mutant defective in Ras GTPase activating protein activity, reverses miR431 's effect on promoting invasion, Erk phosphorylation, and epithelial-mesenchymal transition of PNETs. (quanterix.com)
  • We show that phosphorylation of synGAP by Ca^(2+)/calmodulin-dependent protein kinase II (CaMKII) decreases its affinity for the PDZ domains as much as 10-fold, measured by surface plasmon resonance. (caltech.edu)
  • Therefore, we hypothesize that phosphorylation by CaMKII reduces synGAP′s ability to restrict binding of other proteins to the PDZ domains of PSD-95. (caltech.edu)
  • Protein phosphorylation is one of the widely used posttranslational modifications that alter protein function in vivo. (stanford.edu)
  • We recently showed phosphorylation of Drosophila Plexin A by cyclic adenosine monophosphate (cAMP)-dependent protein kinase (PKA) and subsequent inhibition of plexin-mediated repulsive guidance. (stanford.edu)
  • This phosphorylation occurs in the active site of the plexin GTPase-activating protein (GAP) domain, which in turn inhibits endogenous GAP activity toward Ras/Rap family small GTP-binding proteins by recruiting the phospho-serine/threonine-binding protein 14-3-3ε. (stanford.edu)
  • These data suggest that PKC may regulate interactions of EWS and other RNA-binding proteins with their RNA targets and that IQ domains may provide a regulatory link between Ca2+ signal transduction pathways and RNA processing. (embl.de)
  • 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)
  • SynGAP is a Ras/Rap GTPase-activating protein (GAP) present in high concentration in postsynaptic densities (PSDs) from mammalian forebrain where it binds to all three PDZ (PSD-95, Discs-large, ZO-1) domains of PSD-95. (caltech.edu)
  • We support this hypothesis by showing that three critical postsynaptic signaling proteins that bind to the PDZ domains of PSD-95 are present at a higher ratio to PSD-95 in PSDs isolated from synGAP heterozygous mice. (caltech.edu)
  • This suggests that the intrinsic GTPase reaction could be an attractive target for anti-cancer drug design. (rcsb.org)
  • 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)
  • The prooncoprotein EWS binds calmodulin and is phosphorylated by protein kinase C through an IQ domain. (embl.de)
  • Cyclic AMP binds to specific locations on the regulatory units of the protein kinase, and causes dissociation between the regulatory and catalytic subunits, thus enabling those catalytic units to phosphorylate substrate proteins. (wikipedia.org)
  • Mouse protein citron, a putative rho/rac effector that binds to the GTP-bound forms of rho and rac. (embl.de)
  • When mutated, p120 Ras GTPase-activating protein binds to Krev-1/rap1a, an integrin β1-mediated cell adhesion and angiogenesis protein. (medscape.com)
  • Herein, we show that miR431 overexpression activates Ras/extracellular signal-regulated kinase (Erk) signaling and promotes epithelial-mesenchymal transition, migration/invasion in vitro , and metastasis in both xenograft and spontaneous mouse models of PNET. (quanterix.com)
  • Here, the Ras-GTPase-activating protein SH3 domain-binding protein 1 (G3BP1) was identified as a potential target of resveratrol, and in vitro binding assay results using resveratrol-conjugated Sepharose 4B beads confirmed their direct binding. (umn.edu)
  • Furthermore, MK-STYX interacts with a key component of stress granules: G3BP-1 (Ras-GTPase activating protein SH3 domain binding protein-1). (wm.edu)
  • Written and edited by experts in the field, this collection from Cold Spring Harbor Perspectives in Medicine covers the recent progress that has been made in understanding Ras biology, how Ras activation leads to tumorigenesis, and ways in which oncogenic Ras signaling may be targeted therapeutically. (cshlpress.com)
  • TBC1D15 activated three novel oncogenic pathways to promote self-renewal, p53 loss, and Nanog transcription in TICs. (nature.com)
  • The oncogenic role of TLR4 activated by endotoxin has been confirmed by others in a different liver tumor model 10 . (nature.com)
  • Ras GTPase-activating-like protein IQGAP1. (embl.de)
  • Recent work showing that some Ras oncoproteins may be effectively inhibited by small molecules is covered, as is work on alternative targets (e.g., enzymes that catalyze posttranslational modifications of Ras) and inhibitors (e.g., nucleic acids). (cshlpress.com)
  • In 1998 a family of cAMP-sensitive proteins with guanine nucleotide exchange factor (GEF) activity was discovered. (wikipedia.org)
  • Regulators of small G-proteins like guanine nucleotide releasing factor GNRP (Ras-GRF) (which contains 2 PH domains), guanine nucleotide exchange proteins like vav, dbl, SoS and Saccharomyces cerevisiae CDC24, GTPase activating proteins like rasGAP and BEM2/IPL2, and the human break point cluster protein bcr. (embl.de)
  • The guanine nucleotide exchange factor Sos (Son-of-sevenless) is a complex multidomain protein that activates the small GTPase Ras (H-Ras, K-Ras, N-Ras, but not functionally distinct R-Ras) in response to receptor tyrosine kinase stimulation. (novusbio.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)
  • 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)
  • 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)
  • Activated ERK1/2 also phosphorylates the GTPase dynamin-related protein (Drp1), which then stimulates mitochondrial fission. (cdc.gov)
  • 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)
  • Moreover, FZKA significantly decreased EZH2 mRNA and protein expression, FZKA reversed the resistance of gefitinib by down-regulation of EZH2 protein. (bvsalud.org)
  • Five regions of the 3' UTR that appear to bind proteins were found, one of which is HuR, a tumor antigen. (wikipedia.org)
  • Because CaM can bind with high affinity to a relatively small alpha-helical region of many proteins, success in clearly defining the essential elements of CaM binding motifs seems feasible and should provide a means of identifying CaM binding proteins. (embl.de)
  • Protein kinase A can also phosphorylate specific proteins that bind to promoter regions of DNA, causing increases in transcription. (wikipedia.org)
  • We have found that the C-terminal systeine residues of smg p21B, rhoA p21, and smg p25A are geranylgeranylated, and that these prenylation are essential for each small G protein to bind to membranes. (nii.ac.jp)
  • The domain family possesses multiple functions including the abilities to bind inositol phosphates, and various proteins. (embl.de)
  • In eukaryotes, cyclic AMP works by activating protein kinase A (PKA, or cAMP-dependent protein kinase ). (wikipedia.org)
  • Further effects mainly depend on cAMP-dependent protein kinase , which vary based on the type of cell. (wikipedia.org)
  • Nucleotide exchange activity of Sos is stimulated by allosteric Ras binding. (novusbio.com)
  • The active subunits catalyze the transfer of phosphate from ATP to specific serine or threonine residues of protein substrates. (wikipedia.org)
  • an enzyme involved in the production of various eicosanoids) expression, by activating integrin collagen receptors. (lu.se)
  • In order to explain the biochemical differences, we analysed the GTPase reaction mechanism with a linear free energy relationships approach. (rcsb.org)
  • Dr. Clapp's group is also interested in the cellular and biochemical functions of an orphan group of proteins that are involved in the heterogenetic disorder Fanconi Anemia. (iu.edu)
  • These cancers can be difficult to treat because Ras oncoproteins have long been considered undruggable. (cshlpress.com)
  • This volume is therefore essential reading for all cancer biologists, cell and molecular biologists, and pharmacologists concerned with understanding and treating Ras-driven cancers. (cshlpress.com)
  • We have purified and characterized several GDP/GTP exchange proteins (GDP dissociation stimulator (GDS) and GDP dissociation inhibitor (GDI)) and GTPase activating Proteins (GAP) for small G proteins. (nii.ac.jp)
  • Ras proteins are key molecular switches in cell signaling pathways that, when activated, trigger cell growth and division. (cshlpress.com)
  • Many investigations have focused on defining the region of interaction between CaM and its cellular targets and the action of CaM on target protein function. (embl.de)
  • 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)
  • Calmodulin (CaM) is recognized as a major calcium sensor and orchestrator of regulatory events through its interaction with a diverse group of cellular proteins. (embl.de)
  • Proteins that regulate vesicle exocytosis cluster at AZs, composing the cytomatrix at the active zone (CAZ). (eneuro.org)
  • Although inhibitory postsynaptic sites lack PSDs, they also consist of complex protein matrices. (frontiersin.org)
  • Publications] Sasaki,T.: 'A mammalian inhibitory GDP/GTP exchange protein(GDI)for smg p25A is active on the yeast SEC4 protein. (nii.ac.jp)
  • More important, the combination of FZKA and gefitinib enhanced the inhibitory effect on EZH2, Snail and EGFR proteins. (bvsalud.org)
  • Pleckstrin, the protein where this domain was first detected, is the major substrate of protein kinase C in platelets. (embl.de)
  • In this research project, we have investigated the C-terminal structures of small G proteins, purified the regulatory proteins for small G proteins, and made monoclonal antibodies against small G proteins and their regulatory proteins. (nii.ac.jp)
  • Pleckstrin homology (PH) domains are small modular domains that occur in a large variety of proteins. (embl.de)
  • Evidence is accumulating that small G proteins are involved in the regulation of cell growth and differentiation. (nii.ac.jp)
  • Most of small G proteins have the unique consensus C-terminal motifs containing at least one cysteine residue. (nii.ac.jp)
  • Small G proteins have two interconvertible forms, GDP-bound inactive and GTP-bound active forms. (nii.ac.jp)
  • Publications] Kaibuchi,K.: 'Molecular cloning and characterization of the stimulatory GDP/GTP exchange protein(GDS)for smg p21s,ras p21ーlike small GTPーbinding proteins. (nii.ac.jp)
  • 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)
  • Cell-fate-determinant molecule NUMB-interacting protein (TBC1D15) is overexpressed and contributes to p53 degradation in TICs. (nature.com)
  • the Sos-mediated Ras-activation and Rac activation differ in composition and stability of the formed complex. (novusbio.com)
  • The integrin dependent COX-2 expression was shown to be mediated through the activation of CD47 and its associated G?i3 protein, which in turn lead to protein kinase C? (lu.se)
  • the Ras GTPase and NF?B activation. (lu.se)
  • COX-2 expression is synonymous with activation of the protein. (lu.se)