Abstract:
:Endocytosis and subsequent lysosomal degradation of activated signalling receptors can attenuate signalling. Endocytosis may also promote signalling by targeting receptors to specific compartments. A key step regulating the degradation of receptors is their ubiquitination. Hrs/Vps27p, an endosome-associated, ubiquitin-binding protein, affects sorting and degradation of receptors. Drosophila embryos mutant for hrs show elevated receptor tyrosine kinase (RTK) signalling. Hrs has also been proposed to act as a positive mediator of TGF-beta signalling. We find that Drosophila epithelial cells devoid of Hrs accumulate multiple signalling receptors in an endosomal compartment with high levels of ubiquitinated proteins: not only RTKs (EGFR and PVR) but also Notch and receptors for Hedgehog and Dpp (TGF-beta related). Hrs is not required for Dpp signalling. Instead, loss of Hrs increases Dpp signalling and the level of the type-I receptor Thickveins (Tkv). Finally, most hrs-dependent receptor turnover appears to be ligand independent. Thus, both active and inactive signalling receptors are targeted for degradation in vivo and Hrs is required for their removal.
journal_name
EMBO Repjournal_title
EMBO reportsauthors
Jékely G,Rørth Pdoi
10.1038/sj.embor.7400019keywords:
subject
Has Abstractpub_date
2003-12-01 00:00:00pages
1163-8issue
12eissn
1469-221Xissn
1469-3178pii
7400019journal_volume
4pub_type
杂志文章相关文献
EMBO REPORTS文献大全abstract::Mitochondrial respiration generates an electrochemical proton gradient across the mitochondrial inner membrane called protonmotive force (PMF) to drive diverse functions and synthesize ATP. Current techniques to manipulate the PMF are limited to its dissipation; yet, there is no precise and reversible method to increa...
journal_title:EMBO reports
pub_type: 杂志文章
doi:10.15252/embr.201949113
更新日期:2020-04-03 00:00:00
abstract::The Nedd4 family E3 ligases are key regulators of cell growth and proliferation and are often misregulated in human cancers and other diseases. The ligase activities of Nedd4 E3s are tightly controlled via auto-inhibition. However, the molecular mechanism underlying Nedd4 E3 auto-inhibition and activation is poorly un...
journal_title:EMBO reports
pub_type: 杂志文章
doi:10.15252/embr.201744454
更新日期:2017-09-01 00:00:00
abstract::The active and inactive X chromosomes have distinct epigenetic marks in somatic nuclei, which undergo reprogramming after transplantation into oocytes. We show that, despite the disappearance of Xist RNA coating in 30 min, the epigenetic memory of the inactive X persists with the precocious appearance of histone H3 tr...
journal_title:EMBO reports
pub_type: 杂志文章
doi:10.1038/sj.embor.7400461
更新日期:2005-08-01 00:00:00
abstract::The hypoxic response in humans is mediated by the hypoxia-inducible transcription factor (HIF), for which prolyl hydroxylases (PHDs) act as oxygen-sensing components. The evolutionary origins of the HIF system have been previously unclear. We demonstrate a functional HIF system in the simplest animal, Trichoplax adhae...
journal_title:EMBO reports
pub_type: 杂志文章
doi:10.1038/embor.2010.170
更新日期:2011-01-01 00:00:00
abstract::Anopheles gambiae, the major vector of human malaria parasite, is an important insect model to study vector-parasite interactions. Here, we developed a simple in vivo double-stranded RNA (dsRNA) knockout approach to determine the function of the mosquito antimicrobial peptide gene Defensin. We injected dsRNA into adul...
journal_title:EMBO reports
pub_type: 杂志文章
doi:10.1093/embo-reports/kvf180
更新日期:2002-09-01 00:00:00
abstract::The crucial role of individual Notch receptors and the mechanism by which they maintain intestinal crypt progenitor cells were assessed by using a series of inducible gut-specific Notch mutant mice. We found that Notch1 and Notch2 receptors function redundantly in the gut, as only simultaneous loss of both receptors r...
journal_title:EMBO reports
pub_type: 杂志文章
doi:10.1038/embor.2008.7
更新日期:2008-04-01 00:00:00
abstract::The denitrosylase S-nitrosoglutathione reductase (GSNOR) has been suggested to sustain mitochondrial removal by autophagy (mitophagy), functionally linking S-nitrosylation to cell senescence and aging. In this study, we provide evidence that GSNOR is induced at the translational level in response to hydrogen peroxide ...
journal_title:EMBO reports
pub_type: 杂志文章
doi:10.15252/embr.202050500
更新日期:2020-11-27 00:00:00
abstract::Epidermal growth factor (EGF) activates the EGF receptor (EGFR) and stimulates its internalization and trafficking to lysosomes for degradation. However, a percentage of EGFR undergoes ligand-independent endocytosis and is rapidly recycled back to the plasma membrane. Importantly, alterations in EGFR recycling are a c...
journal_title:EMBO reports
pub_type: 杂志文章
doi:10.15252/embr.201744034
更新日期:2017-12-01 00:00:00
abstract::GlpF, the glycerol facilitator protein of Escherichia coli, is an archetypal member of the aquaporin superfamily. To assess its structure, recombinant histidine-tagged protein was overexpressed, solubilized in octylglucoside and purified to homogeneity. Negative stain electron microscopy of solubilized GlpF protein re...
journal_title:EMBO reports
pub_type: 杂志文章
doi:10.1093/embo-reports/kvd022
更新日期:2000-08-01 00:00:00
abstract::Ubiquitylation is an essential post-translational modification that regulates numerous cellular processes, most notably protein degradation. Ubiquitin can itself be phosphorylated at nearly every serine, threonine, and tyrosine residue. However, the effect of this modification on ubiquitin function is largely unknown....
journal_title:EMBO reports
pub_type: 杂志文章
doi:10.15252/embr.201540298
更新日期:2015-09-01 00:00:00
abstract::The receptor-evoked Ca(2+) signal is sensed and translated by mitochondria. Physiological cytoplasmic Ca(2+) ([Ca(2+)]c) oscillations result in mitochondrial Ca(2+) ([Ca(2+)]m) oscillations, while large and sustained [Ca(2+)]c increase results in a pathologic increase in basal [Ca(2+)]m and in Ca(2+) accumulation. The...
journal_title:EMBO reports
pub_type: 评论,杂志文章
doi:10.1002/embr.201438446
更新日期:2014-03-01 00:00:00
abstract::Trypanosomes use RNA editing to produce most functional mitochondrial messenger RNA. Precise insertion and deletion of hundreds of uridines is necessary to make full-length cytochrome c oxidase III (COXIII) mRNA. We show that COXIII mRNA can be alternatively edited by a mechanism using an alternative guide RNA to make...
journal_title:EMBO reports
pub_type: 杂志文章
doi:10.1038/sj.embor.7400817
更新日期:2006-11-01 00:00:00
abstract::Aurora B localization to mitotic centromeres, which is required for proper chromosome alignment during mitosis, relies on Haspin-dependent histone H3 phosphorylation and on Bub1-dependent histone H2A phosphorylation--which interacts with Borealin through a Shugoshin (Sgo) intermediate. We demonstrate that Mps1 stimula...
journal_title:EMBO reports
pub_type: 杂志文章
doi:10.1038/embor.2012.93
更新日期:2012-09-01 00:00:00
abstract::In Saccharomyces cerevisiae, genome stability depends on RNases H1 and H2, which remove ribonucleotides from DNA and eliminate RNA-DNA hybrids (R-loops). In Schizosaccharomyces pombe, RNase H enzymes were reported to process RNA-DNA hybrids produced at a double-strand break (DSB) generated by I-PpoI meganuclease. Howe...
journal_title:EMBO reports
pub_type: 杂志文章
doi:10.15252/embr.201745335
更新日期:2018-05-01 00:00:00
abstract::STK38 (also known as NDR1) is a Hippo pathway serine/threonine protein kinase with multifarious functions in normal and cancer cells. Using a context-dependent proximity-labeling assay, we identify more than 250 partners of STK38 and find that STK38 modulates its partnership depending on the cellular context by increa...
journal_title:EMBO reports
pub_type: 杂志文章
doi:10.15252/embr.201948150
更新日期:2019-11-05 00:00:00
abstract::Subcellular organization is yielding to large-scale analysis. Researchers are now applying robust mass-spectrometry-based proteomics methods to obtain an inventory of biochemically isolated organelles that contain hundreds of proteins. High-resolution methods allow accurate protein identification, and novel algorithms...
journal_title:EMBO reports
pub_type: 杂志文章,评审
doi:10.1038/sj.embor.7400780
更新日期:2006-09-01 00:00:00
abstract::The function of protein phosphatase 1 nuclear-targeting subunit (PNUTS)--one of the most abundant nuclear-targeting subunits of protein phosphatase 1 (PP1c)--remains largely uncharacterized. We show that PNUTS depletion by small interfering RNA activates a G2 checkpoint in unperturbed cells and prolongs G2 checkpoint ...
journal_title:EMBO reports
pub_type: 杂志文章
doi:10.1038/embor.2010.134
更新日期:2010-11-01 00:00:00
abstract::Paxillin is a protein containing four LIM domains, and functions in integrin signaling. We report here that two transcripts are generated from the paxillin gene locus in Drosophila; one encodes a protein homolog of the vertebrate Paxillin (DPxn37), and the other a protein with only three LIM domains, partly encoded by...
journal_title:EMBO reports
pub_type: 杂志文章
doi:10.1093/embo-reports/kve178
更新日期:2001-09-01 00:00:00
abstract::The high-mobility-group B (HMGB) chromosomal proteins are characterized by the HMG box, a DNA-binding domain that both introduces a tight bend into DNA and binds preferentially to a variety of distorted DNA structures. The HMGB proteins seem to act primarily as architectural facilitators in the manipulation of nucleop...
journal_title:EMBO reports
pub_type: 杂志文章,评审
doi:10.1038/sj.embor.embor741
更新日期:2003-02-01 00:00:00
abstract::The cytosolic pathogen sensor RIG-I is activated by RNAs with exposed 5'-triphosphate (5'-ppp) and terminal double-stranded structures, such as those that are generated during viral infection. RIG-I has been shown to translocate on dsRNA in an ATP-dependent manner. However, the precise role of the ATPase activity in R...
journal_title:EMBO reports
pub_type: 杂志文章
doi:10.1038/embor.2013.102
更新日期:2013-09-01 00:00:00
abstract::Regulated intramembrane proteolysis of the amyloid precursor-protein (APP) produces both a characterstic amyloid-β peptide that contributes to neuritic plaque formation and neurodegeneration in Alzheimer disease and a small APP intracellular domain (AICD) that transcriptionally activates genes implicated in Alzheimer ...
journal_title:EMBO reports
pub_type: 杂志文章
doi:10.1038/embor.2010.210
更新日期:2011-03-01 00:00:00
abstract::Amino acids are essential for cellular metabolism, and it is important to understand how nutrient supply is coordinated with changing energy requirements during embryogenesis. Here, we show that the amino acid transporter Slc7a5/Lat1 is highly expressed in tissues undergoing morphogenesis and that Slc7a5-null mouse em...
journal_title:EMBO reports
pub_type: 杂志文章
doi:10.15252/embr.201948469
更新日期:2020-01-07 00:00:00
abstract::Metazoans use protein homeostasis (proteostasis) pathways to respond to adverse physiological conditions, changing environment, and aging. The nervous system regulates proteostasis in different tissues, but the mechanism is not understood. Here, we show that Caenorhabditis elegans employs biogenic amine neurotransmitt...
journal_title:EMBO reports
pub_type: 杂志文章
doi:10.15252/embr.202051063
更新日期:2021-01-20 00:00:00
abstract::The Drosophila immune system is able to discriminate between classes of bacteria. Detection of Gram-positive bacteria involves a complex of two pattern recognition receptors: peptidoglycan recognition protein SA (PGRP-SA) and Gram-negative binding protein 1 (GNBP1). These activate the Toll signalling pathway. To defin...
journal_title:EMBO reports
pub_type: 杂志文章
doi:10.1038/sj.embor.7400371
更新日期:2005-04-01 00:00:00
abstract::While the genome sequence and gene content are available for an increasing number of organisms, eukaryotic selenoproteins remain poorly characterized. The dual role of the UGA codon confounds the identification of novel selenoprotein genes. Here, we describe a comparative genomics approach that relies on the genome-wi...
journal_title:EMBO reports
pub_type: 杂志文章
doi:10.1038/sj.embor.7400036
更新日期:2004-01-01 00:00:00
abstract::Growth plasticity is a key mechanism by which plants adapt to the ever-changing environmental conditions. Since growth is a high-energy-demanding and irreversible process, it is expected to be regulated by the integration of endogenous energy status as well as environmental conditions. Here, we show that trehalose-6-p...
journal_title:EMBO reports
pub_type: 杂志文章
doi:10.15252/embr.201947828
更新日期:2019-10-04 00:00:00
abstract::Drosophila ovarian germline stem cells (GSCs) are maintained by the extracellular BMP2/4 orthologue Dpp, which is produced from the surrounding somatic niche. The Dpp signal has a short range; it induces a response in GSCs within the niche, but is rapidly extinguished in their progeny only one cell-diameter away. To e...
journal_title:EMBO reports
pub_type: 杂志文章,评审
doi:10.1038/embor.2011.80
更新日期:2011-06-01 00:00:00
abstract::The mitochondrial matrix protease CLPP plays a central role in the activation of the mitochondrial unfolded protein response (UPR(mt)) in Caenorhabditis elegans Far less is known about mammalian UPR(mt) signaling, although similar roles were assumed for central players, including CLPP To better understand the mammalia...
journal_title:EMBO reports
pub_type: 杂志文章
doi:10.15252/embr.201642077
更新日期:2016-07-01 00:00:00
abstract::Tie2, an endothelial cell-specific receptor kinase, has an important role in tumour angiogenesis. In an attempt to identify peptides that specifically interact with and block the Tie2 pathway, a phage-displayed peptide library was screened on a recombinant Tie2 receptor. One peptide, NLLMAAS, completely abolished the ...
journal_title:EMBO reports
pub_type: 杂志文章
doi:10.1038/sj.embor.7400100
更新日期:2004-03-01 00:00:00
abstract::Signal peptide peptidase (SPP) and the four homologous SPP-like (SPPL) proteases constitute a family of intramembrane aspartyl proteases with selectivity for type II-oriented transmembrane segments. Here, we analyse the physiological function of the orphan protease SPPL2c, previously considered to represent a non-expr...
journal_title:EMBO reports
pub_type: 杂志文章
doi:10.15252/embr.201846449
更新日期:2019-03-01 00:00:00