• A GTPase-activating protein controls Rab5 function in endocytic trafficking. (nih.gov)
  • The inactive GDP bound form is promoted by GTPase-activating proteins (GAPs). (embl.de)
  • RAP1 GTPase activating protein (RAP1GAP). (embl.de)
  • GTPase-activating protein Spa-1. (embl.de)
  • In 2016, an interdisciplinary team of cell biologists and biophysicists in the groups of MPI-CBG directors Marino Zerial and Stephan Grill and their colleagues, including PoL and BIOTEC research group leader Marcus Jahnel, discovered that the small GTPase protein Rab5 could trigger a contraction in EEA1. (innovations-report.com)
  • Strikingly, they discovered that the EEA1 protein could undergo multiple flexibility transition cycles, from rigid to flexible and back again, driven solely by the chemical energy released by its interaction with the GTPase Rab5. (innovations-report.com)
  • Ras superfamily GTPase activation and inactivation occur by canonical nucleotide exchange and GTP hydrolysis mechanisms. (elifesciences.org)
  • In this regard, we have recently shown that efficient activation of Ypk1 by TORC2 requires stimulation of TORC2 by the GTP-bound state of a Rab5 GTPase (Vps21/Ypt51) and that, in turn, Rab5-dependent endocytosis may be a mechanism to down-regulate TORC2 signaling after it has been activated. (berkeley.edu)
  • The GTPase Rab11 regulates endosomal protein trafficking and previous work has shown that loss of Rab11 caused intestinal inflammation and hyperplasia in mice and flies. (sdbonline.org)
  • An additional requirement for endosome fusion is the protein Early Endosome Antigen 1 (EEA1), and its recruitment to the endosome depends on phosphatidylinositol 3-phosphate [PI(3)P] and the Rab5 GTPase. (umassmed.edu)
  • Cdc42 activation is limited temporally and spatially by several GTPase-activating proteins. (rupress.org)
  • A structural feature that distinguishes the Rho proteins from other small GTPases is the so-called Rho insert domain located between a β strand and an α helix within the small GTPase domain [ 1 - 3 ]. (biomedcentral.com)
  • Typically Rho proteins are 190-250 residues long and consist only of the GTPase domain and short terminal C-terminal extensions. (biomedcentral.com)
  • Within their GTPase domains, they share approximately 30% amino acid identity with the Ras proteins and 40-95% identity within the family. (biomedcentral.com)
  • Rho GTPase effectors are a large group of proteins and include actin nucleation promoting molecules, adaptors, as well as kinases. (biomedcentral.com)
  • Patrick A. Lewis ABSTRACT Leucine-rich repeat kinase 2 (LRRK2) is a multidomain scaffolding protein with dual guanosine triphosphatase ( GTPase ) and kinase enzymatic activities, providing this protein with the capacity to regulate a multitude of signalling pathways. (biologists.com)
  • engagement triggers rapid GTP-loading of the small GTPase Rac as a master regulator of cytoskeletal rearrangements and lamellipodia-driven internalization. (biologists.com)
  • Rho GTPase activating protein 10 [S. (gsea-msigdb.org)
  • USP6NL, also named RN-tre, is a GTPase-activating protein involved in control of endocytosis and signal transduction. (aacrjournals.org)
  • In contrast, GTPases which are small proteins have not been viewed as molecular force generators. (innovations-report.com)
  • Both enzymes produce phosphatidylinositol 3,4,5-trisposphate in vivo and are regulated by both heterotrimeric G proteins and small GTPases from the Ras or Rho families. (elsevierpure.com)
  • Rho GTPases represent a family of small GTP-binding proteins involved in cell cytoskeleton organization, migration, transcription, and proliferation. (biomedcentral.com)
  • Rho GTPases work as sensitive molecular switches existing either in an inactive, GDP-bound form or an active GTP-bound form. (biomedcentral.com)
  • In turn, GTP-bound active GTPases can interact with a plethora of different effectors which mediate the different cellular functions of this family of proteins. (biomedcentral.com)
  • Mads Eggert Nielsen (University of Copenhagen, Copenhagen, Denmark) reported that the mere activation from the Rab5 GTPases from the conserved GEF VPS9a by GTP binding is essential for pre- and post-invasive immunity against both a non-adapted and, unexpectedly, an adapted powdery mildew fungus within a. thaliana. (faahinhibitor.com)
  • Small G-proteins, monomeric GTPases, or the RAS (Rat sarcoma) superfamily are a large family of small guanine nucleotide-binding proteins with molecular weights ranging from 20 to 30 kDa [ 1 , 2 ]. (oncotarget.com)
  • They cycle between inactive GDP-bound and activated GTP-bound states, which is controlled by GTP hydrolysis-activating proteins (GAPs). (nih.gov)
  • They associate with microtubule bundles (MICROTUBULES) and are believed to produce mechanical force via a process linked to GTP hydrolysis. (lookformedical.com)
  • A small family of rab GTP-binding proteins that play a key role in membrane trafficking in the late endocytic and autophagic pathways. (bvsalud.org)
  • HLB1 Is a Tetratricopeptide Repeat Domain-Containing Protein That Operates at the Intersection of the Exocytic and Endocytic Pathways at the TGN/EE in Arabidopsis. (ouhsc.edu)
  • Endocytic trafficking dynamically regulates neuronal plasma membrane protein presentation and activity, and plays a central role in excitability and plasticity. (umassmed.edu)
  • Over the course of my dissertation research I investigated endocytic mechanisms regulating two neuronal membrane proteins: the anesthetic-activated potassium leak channel, KCNK3, as well as the psychostimulant-sensitive dopamine transporter (DAT). (umassmed.edu)
  • Taken together, these results demonstrate that novel, non-classical endocytic mechanisms dynamically control the plasma membrane presentation of these two important neuronal proteins. (umassmed.edu)
  • 2014). The effect of ARAP2 on FAs depends on the reduction of Arf6?GTP levels by the Arf6 GAP activity, which Acetaminophen controls Rac1?GTP levels and endocytic traffic of integrins (Chen et al. (bio2009.org)
  • Changes in the overall endocytic flux or in the endocytic regulation of select proteins conceivably can help to counteract adverse environmental conditions. (cell-stress.com)
  • Most naturally occurring proteins and peptides from plants are considered safer than chemical drugs. (edu.in)
  • They preferentially bind and release hydrophobic peptides by an ATP-dependent process and are involved in post-translational PROTEIN TRANSLOCATION. (lookformedical.com)
  • A genetically related subfamily of RAB GTP-BINDING PROTEINS involved in transport from the cell membrane to early endosomes. (wakehealth.edu)
  • Full open access research for "Evidence that the rab5 effector APPL1 mediates APP-βCTF-induced dysfunction of endosomes in Down syndrome and Alzheimer's disease" by S Kim, Y Sato, P S Mohan, C Peterhoff, A Pensalfini, A Rigoglioso, Y Jiang and R A Nixon in Molecular Psychiatry . (neurosciencenews.com)
  • ARAP2 associates with adaptor protein with PH domain, PTB domain and leucine zipper motifs 1 (APPL1) in endosomes (Chen et al. (bio2009.org)
  • 2012). APPL1 is recruited by Rab5 to endosomes involved in traffic of transmembrane receptors including integrins (Miaczynska et al. (bio2009.org)
  • An adaptor protein complex primarily involved in the formation of clathrin-related endocytotic vesicles (ENDOSOMES) at the CELL MEMBRANE. (lookformedical.com)
  • Endosomes internalize macromolecules bound by receptors on the cell surface. (lookformedical.com)
  • The 70 or so members of the Rab subfamily of proteins perform a wide range of important tasks inside cells. (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)
  • A constitutively expressed subfamily of the HSP70 heat-shock proteins. (lookformedical.com)
  • ATP binding cassette subfamily E me. (gsea-msigdb.org)
  • 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)
  • The Wee1 class of protein-tyrosine kinase has an important role in cell cycle control. (berkeley.edu)
  • We investigated control mechanisms that regulate the activity, localization, and stability of Wee1, especially the bud neck-localized protein kinase Hsl1 and its more distant paralogs (Gin4 and Kcc4), in particular their recruitment to septin filaments, which assemble at the presumptive site of cell division. (berkeley.edu)
  • Activation of the pheromone receptor-coupled G protein initiates a four-tiered cascade of protein kinases, ultimately resulting in stimulation of a messenger-activated protein kinase or MAPK (Fus3) that translocates into the nucleus. (berkeley.edu)
  • My results indicate that KCNK3 internalizes in response to Protein Kinase C (PKC) activation, using a novel pathway that requires the phosphoserine binding protein, 14-3-3β, and demonstrates for the first time regulated KCNK3 channel trafficking in neurons. (umassmed.edu)
  • The JNK protein kinase is a member of the MAP kinase group that is activated in response to dual phosphorylation on threonine and tyrosine. (umassmed.edu)
  • The protein kinase activity of these JNK isoforms was measured using the transcription factors ATF2, Elk-1 and members of the Jun family as substrates. (umassmed.edu)
  • Par3 and Par6 bind one another and atypical protein kinase C (aPKC). (rupress.org)
  • FAK can directly bind to the p85 subunit of PI-3-kinase, which leads to the activation and production of the signaling phospholipid PIP3, resulting in the activation of Akt. (bio2009.org)
  • This gene encodes a small GTP-binding protein that belongs to the largest family within the Ras superfamily. (nih.gov)
  • Rho proteins belong to the Ras superfamily. (biomedcentral.com)
  • Ras-related protein Rab-5A is a protein that in humans is encoded by the RAB5A gene. (wikipedia.org)
  • However, no significant difference was observed on the G-protein, RAB5A. (oncotarget.com)
  • FAs are structures composed of clustered transmembrane proteins called integrins that bind to the extracellular matrix and link to the actin cytoskeleton and control cell migration, proliferation, survival and differentiation (Gardel et al. (bio2009.org)
  • The plasma membrane can be envisioned as a central compartment in the cellular adaptation to diverse stress conditions as it shapes the interactions between cells and their environment by harboring an elaborate complement of transmembrane proteins, e.g. transporters, channels, receptors, or adhesion proteins. (cell-stress.com)
  • GAP proteins specific for Rap contain a conserved region of around 200 amino-acid residues, the RapGAP domain. (embl.de)
  • Here we define the precise Rab29 binding region of the LRRK2 Armadillo domain between residues 360-450 and show that this domain, termed 'Site #1', can also bind additional LRRK2 substrates, Rab8A and Rab10. (stanford.edu)
  • These proteins share a core structure, the conserved G-box (GDP/GTP) binding domain, of approximately 170 residues [ 3 ]. (oncotarget.com)
  • The pheromone receptors have seven hydrophobic segments and are coupled to a heterotrimeric G protein. (berkeley.edu)
  • Receptors of this type are ubiquitous and transduce binding of a wide variety of extracellular ligands (peptide hormones, neurotransmitters and other bioactive compounds) into a physiological signal. (berkeley.edu)
  • Only two PI3Ks are directly regulated downstream from G protein-coupled receptors (GPCRs): the class I enzymes PI3Kβ and PI3Kγ. (elsevierpure.com)
  • These pits are the entry route for macromolecules bound by cell surface receptors. (lookformedical.com)
  • In the trans-Golgi network (TGN), phosphorylated lysosomal enzymes bind to M-6-P receptors, which direct the enzymes into clathrin-coated vesicles. (biomedcentral.com)
  • This GST-fusion protein can then be purified from cells via its high affinity for glutathione. (thermofisher.com)
  • All members contain the sequence motifs characteristic of all GTP-binding proteins, bind to GDP and GTP with high affinity. (biomedcentral.com)
  • A synthetic enhancer containing high-affinity Dl-binding sites and Twist binding sites exhibits expression in this region. (sdbonline.org)
  • These stripes are regulated by a 300-bp enhancer (NEE) that contains high-affinity Dl-binding sites, Twist-binding sites, and "generic" E-box sequences that appear to bind ubiquitously distributed bHLH activators (Daughterless and Scute), which are present in the unfertilized egg. (sdbonline.org)
  • The zen promoter region contains high-affinity Dl-binding sites and closely linked "corepressor" sites. (sdbonline.org)
  • The short-term protein trafficking inhibition and long-term effect on plant growth and survival caused by TE1 were fully reversible upon drug washout. (portlandpress.com)
  • Herein, we demonstrate that inhibition of Ca2+/CaM, by using either chemical inhibitors or specific antibodies directed to CaM, results in a profound inhibition of EEA1 binding to endosomal membranes both in live cells and in vitro. (umassmed.edu)
  • The encoded protein can activate transcription through pyrimidine-rich initiator (Inr) elements and E-box motifs. (cancerindex.org)
  • Comparison of the binding activity of the JNK isoforms demonstrated that the JNK proteins differ in their interaction with ATF2, Elk-1 and Jun transcription factors. (umassmed.edu)
  • The Dl and Twist proteins appear to make synergistic contact with the basal transcription complex, so that snail is activated throughout the presumptive mesoderm in response to both peak and high levels of the Dl gradient. (sdbonline.org)
  • Rap small G proteins have been implicated in various cellular processes such as exocytosis, cAMP signalling, cell adhesion and cell proliferation. (embl.de)
  • The cytoskeleton is a highly dynamic network of filamentous proteins that enables the active transport of cellular cargo, transduces force, and when assembled into higher-order structures, forms the basis for motile cellular structures that promote cell movement. (mechanobio.info)
  • The unusually complex regulation of PI3Kβ by small and trimeric G proteins and RTKs leads to a rich landscape of signaling responses at the cellular and organismic levels. (elsevierpure.com)
  • The plasma membrane is not only the first point of encounter for many types of environmental stress, but given the diversity of receptor proteins and their associated molecules also represents the site at which many cellular signal cascades originate. (cell-stress.com)
  • These assist with protein folding and, thereby, help to keep the cellular protein machinery functional in spite of adverse thermal conditions. (cell-stress.com)
  • These cell surface proteins impinge on the vast majority of all cellular functions by mediating nutrient uptake, preserving ion homeostasis and initiating complex signaling cascades in response to extracellular cues. (cell-stress.com)
  • The process of moving proteins from one cellular compartment (including extracellular) to another by various sorting and transport mechanisms such as gated transport, protein translocation, and vesicular transport. (lookformedical.com)
  • These findings implicate the potential role of PCAIs as anticancer agents through their direct interaction with monomeric G-proteins. (oncotarget.com)
  • It is the first motor using two components, two differently sized proteins, Rab5 and EEA1, and is driven by GTP instead of ATP. (innovations-report.com)
  • One example is a molecular motor composed of two proteins, EEA1 and Rab5. (innovations-report.com)
  • The binding of the much smaller Rab5 sends a message along the elongated structure of EEA1, thereby increasing its flexibility, similar to how cooking softens spaghetti. (innovations-report.com)
  • However, the team also hypothesized that EEA1 could switch between a flexible and a rigid state, similar to a mechanical motor motion, simply by interacting with Rab5 alone. (innovations-report.com)
  • With an experimental design to investigate the dynamics of the EEA1 protein in mind, Anupam Singh spent three months at the MPI-CBG in 2019. (innovations-report.com)
  • When I met Joan, I explained to him the idea of measuring the protein dynamics of EEA1. (innovations-report.com)
  • I was delighted to learn that the approach to characterize the EEA1 protein could answer whether EEA1 and Rab5 form a two-component motor, as previously suspected. (innovations-report.com)
  • I realized that the difficulties in obtaining the correct molecules could be solved by modifying the EEA1 protein to allow fluorophores to attach to specific protein regions. (innovations-report.com)
  • Armed with the suitable protein molecules and the valuable support of co-author Janelle Lauer, a senior postdoctoral researcher in Marino Zerial's research group, Joan and Anupam were able characterize the dynamics of EEA1 thoroughly using the advanced laser scanning microscopes provided by the light microscopy facilities at the MPI-CBG and the NCBS. (innovations-report.com)
  • These experiments showed that EEA1 and Rab5 form a GTP-driven two-component motor. (innovations-report.com)
  • The researchers discovered APPL1, a protein unrelated to amyloid precursor protein (APP) despite its similar acronym, directly links βCTF to a second protein, rab5, known to activate the molecular chain of events leading to neurodegeneration. (neurosciencenews.com)
  • Abstract ARAP2 is an Arf GAP that has previously been reported to affect focal adhesions (FAs) by regulating Arf6 and integrin trafficking and to bind to the adaptor proteins APPL1. (bio2009.org)
  • 2009). APPL1 also binds directly to Akt, which inhibits signaling through Akt1 (Broussard et al. (bio2009.org)
  • In its GTP-bound form, Cdc42 binds several effectors that help direct polarized cell growth: repolarizing actin and microtubules, directing polarized exocytosis via this reoriented cytoskeleton and by direct contact with exocytic machinery, and recruiting proteins such as septins that form a boundary restricting the region of cell growth. (rupress.org)
  • Other proteins-known as GAPs-lead to the inactivation of the Rab protein. (elifesciences.org)
  • Ca2+ is an essential requirement in membrane fusion, acting through binding proteins such as calmodulin (CaM). (umassmed.edu)
  • 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)
  • These protein kinases correspond to alternatively spliced isoforms derived from the JNK1, JNK2 and JNK3 genes. (umassmed.edu)
  • However, PI3Kβ is also regulated by direct interactions with receptor tyrosine kinases (RTKs) and their tyrosine phosphorylated substrates, and similar to the class II and III PI3Ks, it binds activated Rab5. (elsevierpure.com)
  • 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)
  • The majority of adaptor proteins exist as multi-subunit complexes, however monomeric varieties have also been found. (lookformedical.com)
  • rab5 GTP-Binding Proteins" is a descriptor in the National Library of Medicine's controlled vocabulary thesaurus, MeSH (Medical Subject Headings) . (wakehealth.edu)
  • What does this gene/protein do? (cancerindex.org)
  • Mammalian tuberin protein, the product of a familial tuberous sclerosis gene which, when deleted, causes begnin tumours. (embl.de)
  • The type II target gene snail contains a series of low-affinity Dl-binding sites, as well as binding sites for the bHLH activator, Twist. (sdbonline.org)
  • First is the disruption of enterocyte polarity based on staining of the FERM domain protein Coracle . (sdbonline.org)
  • The combination of growth factors and RTKs can activate the PI3K/AKT signaling pathway and negatively regulate TSC1/2, promoting Rheb to become GTP loaded, which can activate mTORC1. (biomedcentral.com)
  • Drosophila Gigas protein, an homologue of tuberin involved in regulation of cell cycle. (embl.de)
  • Mammalian tuberin-like protein TULIP. (embl.de)
  • This Antibody was verified by Relative expression to ensure that the antibody binds to the antigen stated. (thermofisher.com)
  • They have been primarily found as components of ADAPTOR PROTEIN COMPLEX 2. (lookformedical.com)
  • A clathrin adaptor protein complex primarily involved in clathrin-related transport at the TRANS-GOLGI NETWORK. (lookformedical.com)
  • An adaptor protein complex found primarily on perinuclear compartments. (lookformedical.com)
  • Loss of Pcs impairs Rab11 localization on the trans-side of Golgi units and induces the cytoplasmic accumulation of post-Golgi vesicles bearing rhabdomere proteins, as observed in Rab11-deficiency. (sdbonline.org)
  • This family member can be activated by the GAP protein RN-Tre, and it is localized to the Golgi complex. (nih.gov)
  • A family of large adaptin protein subunits of approximately 100 kDa in size. (lookformedical.com)
  • A family of proteins that play a role as cofactors in the process of CLATHRIN recycling in cells. (lookformedical.com)
  • A family of large adaptin protein complex subunits of approximately 90-130 kDa in size. (lookformedical.com)
  • A family of medium adaptin protein subunits of approximately 45 KDa in size. (lookformedical.com)
  • DnaJ heat shock protein family (Hsp. (gsea-msigdb.org)
  • guanylate binding protein family me. (gsea-msigdb.org)
  • This enhancer contains a cluster of low-affinity Dl binding sites that restrict expression to the ventral-most regions of early embryos. (sdbonline.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)
  • The long term goal of our research is to elucidate the molecular mechanisms by which proteins are targeted to specific and distinct compartments. (stanford.edu)
  • We have shown that Ypk1, a member of the AGC class of protein kinases conserved from yeast to humans, is the essential target of and activated via phosphorylation by the plasma membrane-associated TORC2 complex. (berkeley.edu)
  • By repeatedly contracting and expanding, this molecular motor functions similarly to a classical Stirling engine and helps to distribute cargo to membrane-bound organelles. (innovations-report.com)
  • Protein expression and function of organic anion transporters in short-term and long-term cultures of Huh7 human hepatoma cells. (cancerindex.org)
  • Cells have a fascinating feature to neatly organize their interior by using tiny protein machines called molecular motors that generate directed movements. (innovations-report.com)
  • The The scarcity of proteins with Golgi-modified glycans the Trans Golgi Network (TGN) in plant cells. (faahinhibitor.com)