Nuclear import receptor characterization nuclear localization signals. Medical search. Frequent questions

To study the role of these potential NES sequences in TRα1 nuclear shuttling, we performed transient transfection of mCherry-tagged fusion proteins in HeLa cells followed by scoring of the intracellular distribution by fluorescence microscopy. (wm.edu)
Phosphorylated tyrosine residues recruit various intracellular adaptor and effector molecules that result in the propagation of growth promoting signal transduction cascades [1] , [2] . (plos.org)
Export and import of mRNA and specific proteins from the nucleus is a key step in intracellular signaling and can lead to cell proliferation or apoptosis. (researchsquare.com)
The protease not only releases small peptides, such as the amyloid-β peptide, which drives Alzheimer's disease pathogenesis, but also intracellular domains, which can have critical functions in nuclear signaling. (cipsm.de)
Characterization of the expression, intracellular localization, and replication complex association of the putative mouse hepatitis virus RNA-dependent RNA polymerase. (microbiologyresearch.org)
The intracellular transfer of information (biological activation/inhibition) through a signal pathway. (lookformedical.com)
Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. (lookformedical.com)

This process leads to the activation of each receptors' tyrosine kinase and the subsequent phosphorylation of tyrosine residues located on their C-terminal tails. (plos.org)
The MRTFs also undergo Rho- and ERK-dependent phosphorylation, but the function of MRTF phosphorylation, and the elements and signals involved in MRTF-A nuclear export are largely unexplored. (elifesciences.org)
We show that Rho-dependent MRTF-A phosphorylation reflects relief from an inhibitory function of nuclear actin. (elifesciences.org)
ERK-mediated S98 phosphorylation inhibits assembly of G-actin complexes on the MRTF-A regulatory RPEL domain, promoting nuclear import. (elifesciences.org)
The bound complex is internalized and translocates into the oocyte nucleus thanks to an SV40 nuclear localization signal, enhanced by an adjacent casein kinase phosphorylation site. (biologists.com)

The BRAF protein is a member of the Raf family of serine threonine kinases, which are part of the Ras/RAF/MEK/ERK mitogen activated protein kinase (MAPK) signal transduction cascade that controls cell proliferation and survival (Fig. 1 ) [ 6 ]. (thno.org)

In the presence of nucleoside triphosphates and the small GTP binding protein Ran, the complex moves into the nuclear pore complex and the importin subunits dissociate. (wikipedia.org)
This was accomplished by designing protein constructs containing mCherry-maltose binding protein (MBP) (to create a fusion protein too large to diffuse through the nuclear pore complexes), the TRα1 hinge region NLS (to allow nuclear import), and each NES motif of interest excluding their overlapping residues. (wm.edu)

Based on this work I won a fellowship from the Korean Federation of Science and Technology Societies to investigate the subcellular localisation of maize auxin biosynthesis at Dankook University in Seoul which lead to a publication that showed for the first time that both steps of the TAA/YUC pathway of auxin biosynthesis can be ER-localised. (brookes.ac.uk)

In vivo treatment of MS-444 inhibited HuR cytoplasmic localization and decreased COX-2 expression in tumors. (oncotarget.com)

Membrane-bound HER receptors activate numerous tumor promoting signaling cascades via this mechanism, including the PI3K/AKT, Ras/Raf/Mek/Erk, PLCγ/PKC, and signal transducer and activator of transcription (STAT) pathways [1] , [2] . (plos.org)
These findings give a comprehensive view of the evolutionary canvas of the Rho family and provide guides for future structure and evolution studies of other components of Rho signaling pathways, in particular regulators of the RhoGEF family. (xenbase.org)

Molecular characterization and gene expression of lhcb5 gene encoding CP26 in the light-harvesting complex II of Chlamydomonas reinhardtii. (bio.net)
GTPases of the Rho family are molecular switches that play important roles in converting and amplifying external signals into cellular effects. (xenbase.org)
NIpredict is a method to predict nuclear import activity based on characterization of NLS-import receptor interaction using molecular interaction energy components (MIECs). (mybiosoftware.com)
In plants, pattern recognition receptors (PRRs) on the membrane surface recognize typical damage- or pathogen-associated molecular patterns (PAMPs). (frontiersin.org)
12. Mitsios N, Gaffney J, Kumar P, Krupinski J, Kumar S, Slevin M. Pathophysiology of acute ischaemic stroke: an analysis of common signalling mechanisms and identification of new molecular targets. (southampton.ac.uk)
Among its various strains, pathovar tomato strain DC3000 ( PstDC3000 ) is asserted to infect the plant host Arabidopsis thaliana and thus, has been accepted as a model system for experimental characterization of the molecular dynamics of plant-pathogen interactions. (biomedcentral.com)

Cellular Signalling. (wikipedia.org)
The MRTFs bind G-actin, and signal-regulated changes in cellular G-actin concentration control their nuclear accumulation. (elifesciences.org)
Different subcellular compartments are suggested to be linked through complex retrograde signaling networks to regulate cellular metal homeostasis. (frontiersin.org)
In light of these findings, precisely how β1 integrin transduces ECM cues via signaling intermediates, and the mechanism by which this translates to cellular responses, need to be addressed. (jneurosci.org)
and mediates signaling between the ECM and the cellular interior. (jneurosci.org)
Liberali studies the dynamics of self-organization, and how cellular signaling dictates its spatial-temporal regulation. (unibas.ch)
Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. (lookformedical.com)
In addition to supplying cellular energy, mitochondria are involved in other tasks, such as signaling , cellular differentiation , and cell death , as well as maintaining control of the cell cycle and cell growth . (wikipedia.org)

Positional cloning demonstrated that HST is the Arabidopsis ortholog of the importin β-like nucleocytoplasmic transport receptors exportin 5 in mammals and MSN5 in yeast. (silverchair.com)
These nucleocytoplasmic transport receptors include proteins that regulate nuclear import (importins), proteins that regulate nuclear export (exportins),and proteins that import some proteins and export others. (silverchair.com)

The ErbB/HER family of receptor tyrosine kinases (RTKs) consists of four family members: the epidermal growth factor receptor (EGFR/ErbB1), HER2 (ErbB2/Neu), HER3 (ErbB3), and HER4 (ErbB4). (plos.org)
DNA-dependent protein kinase catalytic subunit (DNA-PKcs), a key component of the non-homologous end-joining (NHEJ) pathway, is involved in DNA double-strand break repair, immunocompetence, genomic integrity, and epidermal growth factor receptor signaling. (amegroups.org)

The import of proteins containing a nuclear localization signal (NLS) requires the NLS import receptor, a heterodimer of importin alpha and beta subunits also known as karyopherins. (wikipedia.org)
Nuclear targeting of proteins: how many different signals? (wikipedia.org)
Furthermore, GSOs protected cells against GLU-induced apoptosis by reducing the expression of the mitochondrial apoptosis-associated Bcl-2 family effector proteins and protected cells from GLU-induced oxidative damage by increasing the nuclear translocation of Nrf2 and HO-1 expression. (sdbonline.org)
This mitochondrial RNA colocalizes with components of the cytoplasmic machinery that makes and imports nuclear-encoded proteins - that is, a ribosomal protein (S6), a nascent peptide associated protein (NAC), and the translocase in the outer membrane (Tom22). (biomedcentral.com)
Then, proteins encoded by the nuclear genome and destined for the mitochondria will be made close to mitochondrial-encoded proteins so that they can be assembled efficiently into mitochondrial complexes. (biomedcentral.com)
Endocytic/exocytic CELL MEMBRANE STRUCTURES rich in glycosphingolipids, cholesterol, and lipid-anchored membrane proteins that function in ENDOCYTOSIS (potocytosis), transcytosis, and SIGNAL TRANSDUCTION. (lookformedical.com)

2002. The accidental sinking of the nuclear submarine, the Kursk: monitoring of radioactivity and the preliminary assessment of the potential impact of radioactive releases. (cdc.gov)

Figure 2: Retrograde signalling via the JUN kinase pathway after an axonal lesion. (nature.com)
RNA-seq results indicated that CSE1L activated the MAPK signaling pathway in NSCLC cells by increasing activity of P65. (researchsquare.com)
CSE1L promotes proliferation of NSCLC cells by activating the MAPK signaling pathway and inhibiting apoptosis in coordination with P65. (researchsquare.com)
Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. (lookformedical.com)
for example, protein kinase activation is part of the platelet activation signal pathway. (lookformedical.com)

Animal steroid hormones initiate signaling by passive diffusion into cells and binding to their nuclear receptors to regulate gene expression. (biologists.com)
We further show that both KdmB and RpdA regulate H3K4me3 and H3K9me3 levels, while RpdA also acts on H3K14ac levels in nuclear extracts. (bvsalud.org)

Brand TM, Iida M, Luthar N, Wleklinski MJ, Starr MM, Wheeler DL (2013) Mapping C-Terminal Transactivation Domains of the Nuclear HER Family Receptor Tyrosine Kinase HER3. (plos.org)
Laminin-5-integrin interaction signals through PI 3-kinase and Rac1b to promote assembly of adherens junctions in HT-29 cells. (xenbase.org)
Integrin-linked kinase (ILK) is a major structural adaptor protein governing signaling complex formation and cytoskeletal dynamics. (jneurosci.org)
This study demonstrated that the Receptor for Activated C-Kinase 1 (RACK1) is important in SC function. (sdbonline.org)

A signal sequence domain essential for processing, but not import, of mitochondrial pre-ornithine carbamyl transferase. (mcmaster.ca)
Previous analyses of dopaminergic (DAergic) neurons from patients with Lewy-body pathology revealed a deficiency in nuclear-encoded genes for mitochondrial respiration, many of which are targets for the transcription factor estrogen-related receptor gamma ( Esrrg /ERRγ). (nature.com)
Laser-captured microdissected (LCM) DAergic neurons from postmortem tissue of patients with Lewy-pathology revealed a deficiency in expression for nuclear-encoded genes involved in mitochondrial respiration and function 12 . (nature.com)
in fact, these genes are targets of the transcriptional coactivator and master regulator of transcription of mitochondrial genes peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) 12 . (nature.com)
Direct regulators of nuclear-encoded mitochondrial genes are members of the estrogen-related receptor (ERR) family, encoded by Esrra , Esrrb and Esrrg . (nature.com)
Some causative mutations arise in the nuclear genome (for example, in NDUFS4 , 7 , and 8 in Leigh and Leigh-like syndromes), others in the mitochondrial one. (biomedcentral.com)
Mitochondrial biology, stress signaling and aging-related degenerative diseases. (upstate.edu)

Importins associated with dynein are an important component of retrograde injury signalling complexes and enable transport of direct importin cargoes, such as transcription factors, as well as secondary cargoes that bind scaffolding molecules associated with importins. (nature.com)
Figure 3: Importins and local translation in retrograde injury signalling. (nature.com)

Components of the host's immune system form a network that processes information about molecules with a foreign origin and damage-associated signals, integrating them with developmental and abiotic cues to adapt the plant's responses. (frontiersin.org)
Maps also chart the connectivity between these molecules, elucidating the circuits and signaling processes that give rise to function. (stanford.edu)
JUN amino-terminal kinases (JNKs) and associated scaffolding and activator molecules participate in retrograde injury signalling. (nature.com)
Local translation of axonally localized mRNAs is required for retrograde injury signalling, enabling recruitment of key molecules such as importin β1 to the complex. (nature.com)

thus, long-distance retrograde signalling from axonal lesion sites to the soma and nucleus is required. (nature.com)
Ibanez, C. F. Message in a bottle: long-range retrograde signaling in the nervous system. (nature.com)
Harrington, A. W. & Ginty, D. D. Long-distance retrograde neurotrophic factor signalling in neurons. (nature.com)

Thyroid hormone receptor α1 (TRα1) is a nuclear receptor that is functionally dependent on its nucleocytoplasmic shuttling for gene regulation. (wm.edu)

To better understand the mechanism of NES-H3 and NES-H6-directed shuttling, we performed "RFP-trap" coimmunoprecipitation assays to determine which exportins interact specifically with these signals. (wm.edu)
These data highlight that ESE-1 contains NLS and NES signals that play a critical role in regulating its subcellular localization and function, and that an intact SAR domain mediates MEC transformation exclusively in the cytoplasm, via a novel nontranscriptional mechanism, whereby the SAR motif is accessible for ligand and/or protein interactions. (biomedcentral.com)
While previous publications have established ESE-1's transcription factor function, we have reported that ESE-1 initiates transformation of MECs via a novel non-nuclear, non-transcriptional mechanism [ 13 ]. (biomedcentral.com)

Using a recombinant endonuclease-deficient Cas9-based gene promoter pulldown approach coupled with mass spectrometry, we found that MCUb is upregulated in the T2D heart due to loss of glucose homeostasis regulator nuclear receptor corepressor 2 repression, and chromatin immunoprecipitation assays identified peroxisome proliferator-activated receptor α as a mediator of MCUb gene expression in T2D cardiomyocytes. (diabetesjournals.org)
Immunoreceptor signaling during development, homeostasis, and effector function of T cells and NK cells. (upstate.edu)

Neurons require specialized mechanisms of motor-facilitated signal transport for communication along long axonal distances to the cell body and the nucleus. (nature.com)

Nuclear transport, a signal- and energy-dependent process, takes place through nuclear pore complexes embedded in the nuclear envelope. (wikipedia.org)

In this study, high-resolution confocal light microscopy is used to explore the localisation of SUN3 and SUN4 in the perinuclear region, to explore topology and to study the role of mid-SUNs on endoplasmic reticulum morphology. (brookes.ac.uk)
A recent study showed that mitochondria clustering around the perinuclear region can act as signaling for increased oxidative stress affecting hypoxia inducible promoters [ 12 ]. (hindawi.com)

The ease of motif acquisition simplifies access to basal housekeeping functions, facilitates the co-regulation of multiple biomolecules allowing them to respond in a coordinated manner to changes in the cell state, and supports the integration of multiple signals for combinatorial decision-making. (biomedcentral.com)
Combinatorial signalling and/or temporal or frequency-encoded signalling could be used to assess the injury location and extent of damage. (nature.com)
The emerging picture of a combinatorial signalling system that conveys both spatial and temporal information will help to guide future translational efforts. (nature.com)

Insulin signaling and the regulation of glucose transport. (xenbase.org)

Prior studies show TRα1 localization is influenced by exportins 4, 5, and 7. (wm.edu)

Signal transduction gRABs attention. (xenbase.org)
It binds CHOLESTEROL and is involved in LIPIDS transport, membrane traffic, and SIGNAL TRANSDUCTION. (lookformedical.com)
In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. (lookformedical.com)

Nuclear localized HER family receptor tyrosine kinases (RTKs) have been observed in primary tumor specimens and cancer cell lines for nearly two decades. (plos.org)

Additionally, HIV-1 IN has been shown to play important roles in several other steps during the viral life cycle, including reverse transcription, nuclear import and chromatin targeting. (biomedcentral.com)
Recently, we have discovered a novel nuclear chromatin binding complex (KERS) that contains the JARID1-type histone demethylase KdmB, a putative cohesion acetyl transferase EcoA, a class I type histone deacetylase RpdA and the PHD ring finger reader protein SntB in the model filamentous fungus Aspergillus nidulans. (bvsalud.org)

Both in the case of nucleotide-binding leucine-rich repeat receptors and leucine-rich repeat receptor kinases interaction networks have been extensively characterized. (frontiersin.org)

Cloning and characterization of an active fragment of luciferase from a luminescent marine alga, Pyrocystis lunula. (bio.net)

These changes enhance CPEB3-IPO5 interaction, which consequently accelerates the nuclear import of CPEB3 and promotes its nuclear function. (wikipedia.org)
Computational identification of post-translational modification-based nuclear import regulations by characterizing nuclear localization signal-import receptor interaction. (mybiosoftware.com)

However, the regions of each receptor that confer transcriptional potential remain poorly defined. (plos.org)
To understand how the B 1 and B 2 regions influenced the transcriptional functions of nuclear HER3, we performed cyclin D1 promoter-luciferase assays in which HER3 deleted of the B 1 and B 2 regions was severely hindered in regulating this promoter. (plos.org)
While the classical membrane-bound functions of HER family RTKs have been extensively studied, accumulating data suggest that these receptors can be found in the cell's nucleus where they can function as co-transcriptional activators [4] , [5] . (plos.org)
ESE-1 initiates transformation of MCF-12A cells via a non-transcriptional, cytoplasmic process that is mediated by a unique 40-amino acid serine and aspartic acid rich (SAR) subdomain, whereas, ESE-1's nuclear transcriptional property is required to maintain the transformed phenotype of MCF7, ZR-75-1 and T47D breast cancer cells. (biomedcentral.com)

In eukaryotic cells the genetic material is surrounded by a membrane system called the nuclear envelope (NE). (brookes.ac.uk)
The Nuclear Envelope is a hallmark of eukaryotic cells. (brookes.ac.uk)
The movement of macromolecules across the nuclear membrane is a central feature of the biology of eukaryotic cells. (silverchair.com)
These recent findings provide a coherent mechanistic framework for axon-soma communication in the injured nerve and shed light on the integration of cytoplasmic and nuclear transport in all eukaryotic cells. (nature.com)

MERS-CoV infection did not prevent the IFN-induced nuclear translocation of phosphorylated STAT1, in contrast to infection with SARS-CoV where this block inhibits the expression of antiviral genes. (microbiologyresearch.org)

The results highlight the importance of mid-SUNs as functional components of the ER and outer nuclear membrane. (brookes.ac.uk)
Despite its emerging role as a key structural and signaling platform, the plant NE remains one of the least understood membrane systems. (brookes.ac.uk)
Better understanding of this membrane system involves understanding its physical connections and its signaling and transport functions. (brookes.ac.uk)

Ultimately, these multiple export signals emphasize the meticulous balance between nuclear import and export of TRα1 for its crucial role in gene regulation and metabolism. (wm.edu)

However, results of these assays were inconclusive, and indicate an area for future work in analyzing TRα1-exportin interactions within the context of the full-length receptor. (wm.edu)

However, despite growing biological and clinical significance, little is known about the structural arrangement of this receptor or any of its family members. (uci.edu)

To map the minimal functional nuclear localization (NLS) and nuclear export (NES) signals, we fused in-frame putative NLS and NES motifs between GFP and the SAR domain. (biomedcentral.com)

The current study aimed to map the putative transactivation domains (TADs) of the HER3 receptor. (plos.org)

Importin alpha binds the NLS-containing cargo in the cytoplasm and importin beta docks the complex at the cytoplasmic side of the nuclear pore complex. (wikipedia.org)
Injected intravenously into adult Xenopus females, the protein-DNA complex is rapidly transported through the bloodstream and, within the ovary, the vitellogenin ligand present in the protein binds to the receptors at the surface of the oocytes. (biologists.com)

Williams, Cheyenne, "Characterization of Novel Export Sequences in the Thyroid Hormone Receptor" (2016). (wm.edu)

The HER2 receptor does not bind to any known ligands, however, its dimerization arm is innately positioned in an open conformation. (plos.org)

The combined H3/H6-219-254 fragment and the CRM1-dependent candidate sequence LBD-188-206 did not show significant cytosolic localization when analyzed using quantitative and semi-quantitative scoring. (wm.edu)

Next, we identified full-length nuclear HER3 association and regulation of a 122 bp region of the cyclin D1 promoter. (plos.org)

providing a ligand for the α6β1 integrin receptor expressed by OLs. (jneurosci.org)

Some sequence motifs responsible for import and export of the receptor have been previously identified, but its full range of nuclear export signal (NES) motifs has not been fully defined. (wm.edu)
Both NES-H3 and NES-H6 motifs show significant individual export function of localizing the mCherry-MBP-Hinge nuclear protein to the cytosol. (wm.edu)

To assess the role of NES2 in regulating ESE-1 subcellular localization and subsequent transformation potency, we site-specifically mutagenized NES2, within full-length GFP-ESE-1 and GFP-NES2-SAR reporter constructs. (biomedcentral.com)

We have previously determined the minimal, transferable sequence for a conserved NES in helix 12 of the receptor but the helix 3/helix 6 (H3/H6) bipartite NES, or monopartite NESs, was not fully characterized. (wm.edu)
Members of this family show sequence homology with estrogen receptors but are incapable of being bound by estrogen. (nature.com)

As JNK signalling can have effects that range from neurite growth promotion to cell death induction, multiple regulatory mechanisms are required to ensure specificity of the signal. (nature.com)

Global Transcriptome Characterization and Assembly of the Thermophilic Ascomycete Chaetomium thermophilum. (db-engine.de)

Anatomy28

Organisms15

Chemicals and Drugs92

Analytical, Diagnostic and Therapeutic Techniques and Equipment27

Phenomena and Processes58

Disciplines and Occupations1

Information Science3

Intracellular7

Phosphorylation5

Mitogen-activa1

Binding protein2

Subcellular localisation1

Cytoplasmic localization1

Pathways2

Molecular6

Cellular8

Transport receptors2

Epidermal2

Proteins6

20021

Pathway5

Regulate2

Kinase4

Mitochondrial7

Importins2

Molecules4

Retrograde3

Nucleocytoplasmic1

Mechanism3

Homeostasis2

Neurons1

Complexes1

Perinuclear region2

Combinatorial3

Glucose1

Exportins1

Transduction3

Tumor1

Chromatin2

Kinases1

Cloning1

Interaction2

Transcriptional4

Eukaryotic cells4

Genes1

Membrane3

Gene1

Assays1

Structural1

Functional1

Putative1

Complex2

20161

Bind1

Quantitative1

Regulation1

Ligand1

Motifs2

Subsequent1

Sequence2

Mechanisms1

Assembly1