Guanine nucleotide exchange factors ("GEFs") stimulate the dissociation of the GTP hydrolytic product, GDP, from small GTP-binding proteins, to promote the binding of a new GTP molecule. (justia.com)
This study reveals a noncanonical role of AMP-activated kinase in which the α subunit C-terminal regulatory domain serves as a guanine-nucleotide-exchange factor for Arf6 during glucose deprivation. (biologists.com)
G proteins consist of two functional units, a guanine nucleotide-binding α subunit and a βγ subunit dimer, and are classified according to their α-subunit into four subfamilies: Gs, Gi, Gq, and G12 [ 2 ]. (biomedcentral.com)
After a ligand binds to the GPCR, it activates a heterotrimeric G-protein, which is composed of three subunits: a guanine nucleotide binding α-subunit, and a βγ-heterodimer (98). (pancreapedia.org)
Type I IFN-activated JAK1/TYK2 also induces rapid phosphorylation and activation of insulin receptor substrate 1 (IRS1) and 2 (IRS2), which subsequently bind to the catalytic p85 subunit of PI3K, which is required for the activation of the regulatory p110 subunit of PI3K [ 20 ]. (scientificarchives.com)
In starvation conditions, the reinitiating ribosomes bypass uORFs 2-4 and reinitiate at GCN4 instead, owing to lowered availability of the ternary complex (TC)-comprised of initiation factor 2 (eIF2), GTP, and initiator Met-tRNAi-which binds to the small (40S) ribosomal subunit to assemble a 43S preinitiation complex (PIC). (nih.gov)
Of special interest are the translation initiation factors eIF2, a GTPase that binds methionyl-tRNA to the ribosome, and eIF5B, a second GTPase that catalyzes ribosomal subunit joining in the final step of translation initiation. (nih.gov)
The first step of protein synthesis is binding of the initiator Met-tRNA to the small ribosomal subunit by the factor eIF2, which is composed of three subunits. (nih.gov)
The gamma subunit of eIF2 is a GTPase that resembles the bacterial translation elongation factor EF-Tu. (nih.gov)
Proteins17
G proteins are an important class of regulatory switches in all living systems. (nature.com)
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)
Like the other Vav proteins, Vav3 is phosphorylated (activated) following ligand binding to a variety of receptor tyrosine kinases (TKs), including EGF receptor, PDGF receptor, insulin receptor, and insulin-like growth factor I receptor. (cytoskeleton.com)
The guanine nucleotide exchange factor (GEF) Dbl targets Rho family proteins thereby stimulating their GDP/GTP exchange, and thus is believed to be involved in receptor-mediated regulation of the proteins. (embl-heidelberg.de)
Protein synthesis in mammalian cells is regulated through alterations in the states of phosphorylation of eukaryotic initiation factors and elongation factors (eIFs and eEFs respectively) and of other regulatory proteins. (silverchair.com)
Heterotrimeric guanine nucleotide-binding proteins (G proteins) mediate extracellular signals from transmembrane G protein-coupled receptors (GPCRs) to activate intracellular effector molecules, triggering signaling pathways that lead to a variety of cellular responses [ 1 , 2 ]. (biomedcentral.com)
G proteins constitute a large superfamily of regulatory proteins that show a high similarity in primary structure and organization of the functional center [ 1 - 3 ]. (biomedcentral.com)
The superfamily of G proteins includes three main classes: Ras-like GTPases, G α subunits of heterotrimeric G proteins, and the translation elongation factors. (biomedcentral.com)
This gene encodes a transcription factor belonging to a family of proteins that share homology with the high mobility group protein-1. (cancer-genetics.org)
Epac1 and Epac2 are multi-domain proteins consisting of an N-terminal regulatory region and a C-terminal catalytic region. (researchensemble.com)
These proteins may either trigger the metastatic potential of transformed cells or act as factors that contribute to the transforming activity of oncoproteins. (medicineinnovates.com)
RGA and GAI belong to the DELLA subfamily within the GRAS family of plant regulatory proteins. (nih.gov)
In genetic and biochemical studies, we found that the mutation disrupts eIF2 complex integrity, impairs general translation, alters translational control of mRNAs encoding key regulatory proteins, and reduces the fidelity of translation start codon selection. (nih.gov)
Binding to cAMP, the nucleotide cyclic AMP (adenosine 3',5'-cyclophosphate). (mcw.edu)
Cyclic nucleotides, like other nucleotides, are composed of three functional groups: a ribose sugar, a nitrogenous base, and a single phosphate group. (pancreapedia.org)
A cyclic nucleotide, unlike other nucleotides, has a cyclic bond arrangement between the ribose sugar and the phosphate group. (pancreapedia.org)
There are two main groups of cyclic nucleotides: the canonical or well-established and the non-canonical or unknown-function cyclic nucleotides. (pancreapedia.org)
The two well-established cyclic nucleotides are adenosine-3',5'-cyclic monophosphate (cyclic AMP) and guanine-3',5'-cyclic monophosphate (cyclic GMP). (pancreapedia.org)
The non-canonical cyclic nucleotides include the purines inosine-3',5'-cyclic monophosphate (cyclic IMP), xanthosine-3',5'-cyclic monophosphate (cyclic XMP) and the pyrimidines cytidine-3',5'-cyclic monophosphate (cyclic cCMP), uridine-3',5'-cyclic monophosphate (cyclic UMP), and thymidine-3',5'-cyclic monophosphate (cTMP) (145). (pancreapedia.org)
A cyclase enzyme (lyase) catalyzes the formation of the cyclic nucleotide from its nucleotide triphosphate precursor ( Figure 1 ). (pancreapedia.org)
Cyclic nucleotides form when the phosphate group of the molecule of nucleotide triphosphate (ATP or GTP) is attacked by the 3' hydroxyl group of the ribose, forming a cyclic 3',5'-phosphate ester with release of pyrophosphate. (pancreapedia.org)
Cyclic nucleotide signaling can be initiated by two general mechanisms. (pancreapedia.org)
The end products of this catalytic reaction are a cyclic nucleotide (cyclic AMP or cyclic GMP) and a pyrophosphate group. (pancreapedia.org)
Sperm intracellular cAMP levels depend on the activity of adenylyl cyclases, mostly SACY, though transmembrane-containing adenylyl cyclases are also present, and on the activity of cyclic nucleotide phosphodiesterases (PDE) whose role is to degrade cAMP into 5'-AMP. (plos.org)
Goupil S, Maréchal L, El Hajj H, Tremblay M-È, Richard FJ, Leclerc P (2016) Identification and Localization of the Cyclic Nucleotide Phosphodiesterase 10A in Bovine Testis and Mature Spermatozoa. (plos.org)
Epac3
In vitro studies suggest that cAMP relieves the interaction between the regulatory and catalytic domains of Epac. (ox.ac.uk)
Epac protein, activated by cAMP, catalyzes the exchange of GTP in the GDP form. (wada-ama.org)
abstract = "Autosomal recessive mutations in eukaryotic initiation factor 2B (eIF2B) cause leukoencephalopathy vanishing white matter with a wide clinical spectrum. (amsterdamumc.org)
We identified the eIF2α phosphatases in yeast and made key contributions to elucidating the mechanism whereby phosphorylated eIF2 inhibits its GDP-GTP exchange factor, eIF2B, defining the catalytic and regulatory subcomplexes of eIF2B and their distinct roles in binding phosphorylated or nonphosphorylated eIF2. (nih.gov)
TC abundance is reduced in starved cells by phosphorylation of eIF2α by Gcn2, converting eIF2 from substrate to inhibitor of its guanine nucleotide exchange factor (GEF) eIF2B. (nih.gov)
Phosphorylation of eIF2alpha converts eIF2 from a substrate to an inhibitor of its guanine-nucleotide exchange factor eIF2B. (nih.gov)
The inhibition of eIF2B impairs general translation, slowing the growth of yeast cells and, paradoxically, enhancing the translation of the GCN4 mRNA (GCN4 is a transcription factor) required for yeast cells to grow under amino-acid starvation conditions. (nih.gov)
GTPase5
These regions and the phosphate-binding loop of the GTPase interact with the phosphates of the nucleotide and a coordinating magnesium ion to maintain high affinity binding of the nucleotide. (wikipedia.org)
cells the critical NPF underlying lamellipodium formation is the WRC WAVE [WASP (Wiskott-Aldrich syndrome protein)-family verprolin-homologous protein] regulatory complex which is thought to be activated at the plasma membrane by the Rho GTPase Rac1 (Kunda et al. (biodiversityhotspot.org)
Four mutant complementation groups were characterized that correspond to respective mutations in genes encoding Ran (gsp1), and essential Ran regulatory factors Ran GTPase-activating protein (rna1), Ran guanine nucleotide exchange factor (prp20), and the RanGDP import factor (ntf2). (tamu.edu)
Blocking Arf79F activation with guanine nucleotide exchange factor inhibitors impaired WRC localisation to the plasma membrane and concomitant generation of lamellipodia. (biodiversityhotspot.org)
Future research will aim at identifying specific inhibitors and/or inducers of UPR regulatory markers as well as expand the list of UPR-related animal models. (molvis.org)
GTPases3
GTPases contain two loops called switch 1 and switch 2 that are situated on either side of the bound nucleotide. (wikipedia.org)
Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases Also called Dbl-homologous (DH) domain. (embl-heidelberg.de)
However, despite a well characterized role of Rho GTPases, the potential role of secreted factors in the capacity of G12 signaling to promote invasion of cancer cells is just beginning to be addressed. (biomedcentral.com)
EIF23
genes EIF2B1, 2, 3, 4 and 5) and is the guanine nucleotide-exchange factor (GEF) for eIF2. (amsterdamumc.org)
Early accomplishments of the SNCGE in this area include discovering the novel regulatory mechanism that induces translation of GCN4 mRNA via small upstream ORFs (uORFs) in the mRNA leader by phosphorylation and inhibition of eIF2 by the kinase Gcn2, now understood to regulate expression of key transcription factors (Atf4 and Atf5) in mammals and implicated in learning and memory. (nih.gov)
We also made key contributions to identifying the eIF2α kinase Gcn2 and elucidating its regulation by amino acids, via allosteric control of kinase activity by uncharged tRNAs and Gcn2 regulatory domains, and by the TOR pathway through Gcn2-Ser577 phosphorylation. (nih.gov)
Genes4
The other two elongation factors, SseEF1A3 and SseEF1A4 , represent novel genes that are mainly expressed in gills and skin. (biomedcentral.com)
Type I IFN- activated STAT1 can also form a homodimer known as IFNγ-Activated Factor (GAF), which migrates into the nucleus, and binds to IFNγ-Activated Sequences (GAS), to induce proinflammatory genes [ 10 , 11 ]. (scientificarchives.com)
MicroRNAs (miRNAs) are short (about 21 nucleotides long) strands of non-coding RNA that regulate the expression of multiple genes [ 1 ]. (biomedcentral.com)
Knockdown experiments of FOXM1 and MYBL2 suggest that these factors regulate genes involved in controlling cell cycle progression and cell division. (prolekarniky.cz)
Stabilize1
A Ras exchange motif (REM) domain acts as an intramolecular bridge between the regulatory and the catalytic regions to stabilize the guanine nucleotide exchange (GEF) domain name. (researchensemble.com)
Ribosylation factor1
Morinaga, N., Tsai, S.-C., Moss, J. & Vaughan, M. Isolation of a brefeldin A-inhibited guanine nucleotide-exchange protein for ADP ribosylation factor (ARF) 1 and ARF3 that contains a Sec7-like domain. (nature.com)
Rac12
Vav3 GTP Exchange Factor (GEF) of Rac1, RhoA and Cdc42. (cytoskeleton.com)
2010 suggested that additional unknown factors are required to facilitate WRC-dependent actin polymerisation (Davidson and Insall 2011 We showed that active Rac1 was indeed insufficient for recruitment and activation of the WRC at the membrane in mammalian cell extract (Koronakis et al. (biodiversityhotspot.org)
Transcription factor4
This transcription factor is involved in the Wnt signaling pathway, and it may function in hair cell differentiation and follicle morphogenesis. (cancer-genetics.org)
We analyzed the role of transcription factor Zfx, a recently identified regulator of stem cell maintenance, in B cell development and homeostasis. (gsea-msigdb.org)
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)
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)
Recent studies have uncovered key intrinsic mechanisms by which TNF acts on osteoclast precursors to restrain osteoclastogenesis, including the mechanisms mediated by RBP-J signaling, RBP-J and ITAM (Immunoreceptor tyrosine-based activation motif) crosstalk, RBP-J mediated regulatory network, NF- κ B p100, IRF8, and Def6. (frontiersin.org)
Bound1
Helms, J. B. & Rothman, J. E. Inhibition by brefeldin A of a Golgi membrane enzyme that catalyses exchange of guanine nucleotide bound to ARF. (nature.com)
We are characterizing eIF2gamma mutations that are associated with a novel X-linked intellectual disability syndrome, and we are investigating the function of the translation factor eIF5A with a focus on its ability to stimulate the peptidyl transferase activity of the ribosome and facilitate the reactivity of poor substrates such as proline. (nih.gov)
Golgi1
Donaldson, J. G., Finazzi, D. & Klausner, R. D. Brefeldin A inhibits Golgi membrane-catalysed exchange of guanine nucleotide onto ARF protein. (nature.com)
Amino acid1
As a sub-objective, since PDE10A transcript variants were reported strictly through analyses of bovine genomic sequence, we also wanted to determine the nucleotide and amino acid sequences by experimental evidence. (plos.org)
Receptor1
Homeostatic osteoclastogenesis is effectively induced by RANKL (Receptor activator of nuclear factor kappa-B ligand). (frontiersin.org)
Mediate1
MiR-155 also upregulates Mxd1/Mad1, a network of basic helix-loop-helix leucine zipper transcription factors which mediate cellular proliferation, differentiation, and apoptosis, through regulating BCL6. (biomedcentral.com)
Eukaryotic translation2
Eukaryotic elongation factor 1 alpha (eEF1A) is one of the four subunits composing eukaryotic translation elongation factor 1. (biomedcentral.com)
The eukaryotic translation elongation factor 1 alpha, currently termed eEF1A, is a member of the G protein family, and one of the four subunits that compose the eukaryotic elongation factor 1 [ 5 , 6 ]. (biomedcentral.com)
Family2
Jackson, C. L. & Casanova, J. E. Turning on ARF: the Sec7 family of guanine-nucleotide-exchange factors. (nature.com)
The Vav family of Rho/Rac guanosine nucleotide exchange factors comprises three members in mammalian cells. (biomedcentral.com)
Activity1
A variety of unrelated structural domains have been shown to exhibit guanine nucleotide exchange activity. (wikipedia.org)
Activation2
Furthermore, the enhanced expression of these secreted factors was found to be facilitated by the activation of their corresponding promoters, where NF-κB seems to be one of the major regulators. (biomedcentral.com)
Our group discovered the Gcn2 positive effectors Gcn1 and Gcn20 and the importance of ribosomal Gcn1/Gcn20/Gcn2 regulatory complexes in Gcn2 activation. (nih.gov)
Domain1
The N-terminal regulatory domain name bears a disheveled, Egl-10, pleckstrin (DEP) domain name implicated in membrane association and a high-affinity cAMP-binding domain name (cAMP-B). Epac2 additionally contains a second low-affinity cAMP-A domain name of uncertain biological function. (researchensemble.com)
Targets1
These studies confirm and extend findings that secreted factors contribute to the oncogenic potential of G12 signaling, and suggest potential therapeutic targets to control this process. (biomedcentral.com)
Vav31
The major isoforms produced from the alternative splicing of Vav3 include full-length Vav3-alpha and N-terminal truncated Vav3.1 (which lack self-regulatory domains). (medicineinnovates.com)
Binding2
In doing so, this GEF-facilitated exchange of GDP for GTP is associated with structural changes in the GTP-binding protein which influence the degree to which the GTP-binding protein can interact with other molecules. (justia.com)
Epac1 is a guanine nucleotide exchange factor for Rap1 that is activated by direct binding of cAMP. (ox.ac.uk)
Gene2
Activated STAT1 and STAT2 monomers dimerize and interact with IRF9 (IFN-regulatory factor 9) in the cytoplasm, which is known as the ISGF3 (IFN-stimulated gene (ISG) factor 3) complex [ 1 , 7 ]. (scientificarchives.com)
We are also examining the role of the hypusine modification on eIF5A and the role of this factor in gene-specific translational control mechanisms. (nih.gov)
Role4
TNF (Tumor necrosis factor) is a pleiotropic cytokine that plays an important role in immunity and inflammatory bone destruction. (frontiersin.org)
Bioinformatics analysis of the promoter elements of the identified factors suggested NF-κB elements played a role in their enhanced expression, which was tested by chromatin immunoprecipitation. (biomedcentral.com)
We found that signaling through the Gα12 in MDA-MB-231 and MCF10A breast cancer cell lines enhances expression of interleukins (IL)-6 and −8, and matrix metalloproteinase (MMP)-2, and that these secreted factors play a role in G12-stimulated cell invasion. (biomedcentral.com)
TU and T4 treatments demonstrate that SseEF1A4 is up-regulated by THs, suggesting a role in the translational regulation of the factors involved in the dramatic changes that occurs during Senegalese sole metamorphosis. (biomedcentral.com)
Regulation1
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)
Complex2
The WAVE regulatory complex (WRC) drives the polymerisation of actin filaments located beneath the plasma membrane to generate lamellipodia that are pivotal to cell architecture and movement. (biodiversityhotspot.org)
ii) identifying a higher-order assembly of initiation factors 1, 2, 3, and 5-the multifactor complex (MFC)-and elucidating its roles in PIC assembly and accurate start codon selection. (nih.gov)
Small1
This protein is an exchange factor (guanine nucleotide) for the small G protein Rap. (wada-ama.org)
Yeast1
We use molecular-genetic and biochemical studies in yeast and human cells to dissect the structure-function properties of translation factors. (nih.gov)