The E3 ligase RNF43 inhibits Wnt signaling downstream of mutated β-catenin by sequestering TCF4 to the nuclear membrane.

abstract：:The vascular endothelial growth factor (VEGF) signaling pathway plays a pivotal role in normal development and also represents a major therapeutic target for tumors and intraocular neovascular disorders. The VEGF receptor tyrosine kinases promote angiogenesis by phosphorylating downstream proteins in endothelial cells...

journal_title：Science signaling

authors： Zhuang G,Yu K,Jiang Z,Chung A,Yao J,Ha C,Toy K,Soriano R,Haley B,Blackwood E,Sampath D,Bais C,Lill JR,Ferrara N

更新日期：2013-04-16 00:00:00

abstract：:Adenosine 5'-diphosphate (ADP)-ribosylation is a protein posttranslational modification that is catalyzed by ADP-ribosyltransferases (ARTs), using nicotinamide adenine dinucleotide (NAD(+)) as a substrate. Mono-ribosylation can be extended into polymers of ADP-ribose (PAR). Poly(ADP-ribosyl)polymerase (PARP) 1, the be...

journal_title：Science signaling

authors： Hottiger MO,Boothby M,Koch-Nolte F,Lüscher B,Martin NM,Plummer R,Wang ZQ,Ziegler M

更新日期：2011-05-24 00:00:00

abstract：:The mitogen-activated protein kinase (MAPK) extracellular signal-regulated kinase 2 (ERK2) is ubiquitously expressed in mammalian tissues and is involved in a wide range of biological processes. Although MAPKs have been intensely studied, identification of their substrates remains challenging. We have optimized a chem...

journal_title：Science signaling

authors： Carlson SM,Chouinard CR,Labadorf A,Lam CJ,Schmelzle K,Fraenkel E,White FM

更新日期：2011-10-25 00:00:00

abstract：:The TRAF [tumor necrosis factor receptor-associated factor] family of cytoplasmic adaptor proteins link cell-surface receptors to intracellular signaling pathways that regulate innate and adaptive immune responses. In response to activation of RIG-I (retinoic acid-inducible gene I), a component of a pattern recognitio...

journal_title：Science signaling

authors： Zhang P,Reichardt A,Liang H,Aliyari R,Cheng D,Wang Y,Xu F,Cheng G,Liu Y

更新日期：2012-11-13 00:00:00

abstract：:Type I interferons (IFNs), including various IFN-α isoforms and IFN-β, are a family of homologous, multifunctional cytokines. IFNs activate different cellular responses by binding to a common receptor that consists of two subunits, IFNAR1 and IFNAR2. In addition to stimulating antiviral responses, they also inhibit ce...

journal_title：Science signaling

authors： Levin D,Schneider WM,Hoffmann HH,Yarden G,Busetto AG,Manor O,Sharma N,Rice CM,Schreiber G

更新日期：2014-05-27 00:00:00

abstract：:Over the last 50 years, the posttranslational modification (PTM) of proteins has emerged as a central mechanism for cells to regulate metabolism, growth, differentiation, cell-cell interactions, and immune responses. By influencing protein structure and function, PTM leads to a multiplication of proteome diversity. Re...

journal_title：Science signaling

authors： Rudolph TK,Freeman BA

更新日期：2009-09-29 00:00:00

abstract：:Morphogens form concentration gradients that organize patterns of cells and control growth. It has been suggested that, rather than the intensity of morphogen signaling, it is its gradation that is the relevant modulator of cell proliferation. According to this view, the ability of morphogens to regulate growth during...

journal_title：Science signaling

authors： Baena-Lopez LA,Franch-Marro X,Vincent JP

更新日期：2009-10-06 00:00:00

abstract：:The European Molecular Biology Organization (EMBO) meeting Visualizing Immune System Complexity, held in January 2009, covered multiple scales, from imaging single molecules to imaging whole animals. In addition to experimental details, there was an emphasis on modeling both for data analysis and as a predictive tool ...

journal_title：Science signaling

authors： Dustin ML

更新日期：2009-04-14 00:00:00

abstract：:Mutations in AMPA receptor recycling machinery underlie cognitive impairment in an intellectual disorder and in neurodegenerative diseases. ...

journal_title：Science signaling

authors： Ferrarelli LK

更新日期：2017-05-02 00:00:00

abstract：:Chemoattractants induce cell migration through the activation of a distinct family of structurally related heterotrimeric guanine nucleotide-binding protein (G protein)-coupled receptors. Over the past few years, several receptors in this family have been identified that recognize different classes of chemoattractants...

journal_title：Science signaling

authors： Borroni EM,Bonecchi R,Mantovani A,Locati M

更新日期：2009-02-24 00:00:00

abstract：:The beta-amyloid (Abeta) peptide is associated with the pathogenesis of Alzheimer's disease (AD). Evidence gathered over the last two decades suggests that the gradual accumulation of soluble and insoluble Abeta peptide species triggers a cascade of events that leads to the clinical manifestation of AD. Abeta accumula...

journal_title：Science signaling

authors： Thathiah A,De Strooper B

更新日期：2009-10-20 00:00:00

abstract：:DNAX-activating protein of 12 kD (DAP12) is an immunoreceptor tyrosine-based activation motif (ITAM)-containing adaptor protein found in myeloid cells and natural killer cells, and it couples to various receptors that mediate either cellular activation or inhibition. DAP12 inhibits Toll-like receptor (TLR) signaling, ...

journal_title：Science signaling

authors： Peng Q,Long CL,Malhotra S,Humphrey MB

更新日期：2013-08-20 00:00:00

abstract：:Postsynaptic organizational protein complexes play central roles both in orchestrating synapse formation and in defining the functional properties of synaptic transmission that together shape the flow of information through neuronal networks. A key component of these organizational protein complexes is the family of s...

journal_title：Science signaling

authors： Ali H,Marth L,Krueger-Burg D

更新日期：2020-12-22 00:00:00

abstract：:The mechanisms that determine localized formation of reactive oxygen species (ROS) through NADPH (reduced form of nicotinamide adenine dinucleotide phosphate) oxidase (Nox) family members in nonphagocytic cells are unknown. We show that the c-Src substrate proteins Tks4 (tyrosine kinase substrate with four SH3 domains...

journal_title：Science signaling

authors： Gianni D,Diaz B,Taulet N,Fowler B,Courtneidge SA,Bokoch GM

更新日期：2009-09-15 00:00:00

abstract：:Cytosolic pattern recognition receptors (PRRs) sense intracellular nucleic acids from pathogens such as bacteria and viruses, which leads to the induction of type I interferon (IFN) responses that are essential for an effective immune response. Further, these PRR pathways can be aberrantly activated by self DNA, which...

journal_title：Science signaling

authors： Bowie A

更新日期：2012-03-06 00:00:00

abstract：:Skeletal muscle mass is regulated by activity, metabolism, and the availability of nutrients. During muscle atrophy, MNK2 expression increases. We found that MNK2 (mitogen-activated protein kinase-interacting kinase 2), but not MNK1, inhibited proteins involved in promoting protein synthesis, including eukaryotic tran...

journal_title：Science signaling

authors： Hu SI,Katz M,Chin S,Qi X,Cruz J,Ibebunjo C,Zhao S,Chen A,Glass DJ

更新日期：2012-02-14 00:00:00

abstract：:Precise control of the activity and abundance of ubiquitin-conjugating enzymes (E2s) ensures fidelity in ubiquitin chain synthesis. In this issue of Science Signaling, Liess et al. demonstrate that the human anaphase-promoting complex (APC/C)-associated E2 UBE2S adopts an autoinhibited dimeric state that increases the...

journal_title：Science signaling

authors： Bremm A

更新日期：2020-10-20 00:00:00

abstract：:Precise regulation of nuclear factor κB (NF-κB) signaling is crucial for normal immune responses, and defective NF-κB activity underlies a range of immunodeficiencies. NF-κB is activated through two signaling cascades: the classical and noncanonical pathways. The classical pathway requires inhibitor of κB kinase β (IK...

journal_title：Science signaling

authors： Gray CM,Remouchamps C,McCorkell KA,Solt LA,Dejardin E,Orange JS,May MJ

更新日期：2014-02-04 00:00:00

abstract：:MKK4 (mitogen-activated protein kinase kinase 4) is a pivotal upstream activator of c-Jun N-terminal kinase and p38. Here, we report that the abundance of MKK4 increases in senescent human diploid fibroblasts through enhanced translation. We identified four microRNAs (miR-15b, miR-24, miR-25, and miR-141) that target ...

journal_title：Science signaling

authors： Marasa BS,Srikantan S,Masuda K,Abdelmohsen K,Kuwano Y,Yang X,Martindale JL,Rinker-Schaeffer CW,Gorospe M

更新日期：2009-10-27 00:00:00

abstract：:The postsynaptic site of neurons is composed of more than 1500 proteins arranged in protein-protein interaction complexes, the composition of which is modulated by protein phosphorylation through the actions of complex signaling networks. Components of these networks function as key regulators of synaptic plasticity, ...

journal_title：Science signaling

authors： Li J,Wilkinson B,Clementel VA,Hou J,O'Dell TJ,Coba MP

更新日期：2016-08-09 00:00:00

abstract：:The protein kinase ATM is a master regulator of the DNA damage response but also responds directly to oxidative stress. Loss of ATM causes ataxia telangiectasia, a neurodegenerative disorder with pleiotropic symptoms that include cerebellar dysfunction, cancer, diabetes, and premature aging. We genetically separated t...

journal_title：Science signaling

authors： Lee JH,Mand MR,Kao CH,Zhou Y,Ryu SW,Richards AL,Coon JJ,Paull TT

更新日期：2018-01-09 00:00:00

abstract：:Cellular dedifferentiation, the transition of differentiated somatic cells to pluripotent stem cells, ensures developmental plasticity and contributes to wound healing in plants. Wounding induces cells to form a mass of unorganized pluripotent cells called callus at the wound site. Explanted cells can also form callus...

journal_title：Science signaling

authors： Lee K,Park OS,Seo PJ

更新日期：2017-11-28 00:00:00

abstract：:Slit proteins act as repulsive axon guidance cues by activating receptors of the Roundabout (Robo) family. During early neurogenesis in Drosophila melanogaster, Slit prevents the growth cones of longitudinal tract neurons from inappropriately crossing the midline, thus restricting these cells to trajectories parallel ...

journal_title：Science signaling

authors： Manavalan MA,Jayasinghe VR,Grewal R,Bhat KM

更新日期：2017-06-20 00:00:00

abstract：:Although many anticancer drugs that target receptor tyrosine kinases (RTKs) provide clinical benefit, their long-term use is limited by resistance that is often attributed to increased abundance or activation of another RTK that compensates for the inhibited receptor. To uncover common and unique features in the signa...

journal_title：Science signaling

authors： Wagner JP,Wolf-Yadlin A,Sevecka M,Grenier JK,Root DE,Lauffenburger DA,MacBeath G

更新日期：2013-07-16 00:00:00

abstract：:Biophysical methods and x-ray crystallography have revealed that class A G protein-coupled receptors (GPCRs) can form homodimers. We combined computational approaches with receptor cross-linking, energy transfer, and a newly developed functional export assay to characterize the residues involved in the dimerization in...

journal_title：Science signaling

authors： Jin J,Momboisse F,Boncompain G,Koensgen F,Zhou Z,Cordeiro N,Arenzana-Seisdedos F,Perez F,Lagane B,Kellenberger E,Brelot A

更新日期：2018-05-08 00:00:00

abstract：:Netrin-1 displays proto-oncogenic activity in several cancers, which is thought to be due to the ability of this secreted cue to stimulate survival when bound to its receptors. We showed that in contrast to full-length, secreted netrin-1, some cancer cells produced a truncated intranuclear form of netrin-1 (ΔN-netrin-...

journal_title：Science signaling

authors： Delloye-Bourgeois C,Goldschneider D,Paradisi A,Therizols G,Belin S,Hacot S,Rosa-Calatrava M,Scoazec JY,Diaz JJ,Bernet A,Mehlen P

更新日期：2012-08-07 00:00:00

abstract：:Birth defects of the heart and face are common, and most have no known genetic cause, suggesting a role for environmental factors. Maternal fever during the first trimester is an environmental risk factor linked to these defects. Neural crest cells are precursor populations essential to the development of both at-risk...

journal_title：Science signaling

authors： Hutson MR,Keyte AL,Hernández-Morales M,Gibbs E,Kupchinsky ZA,Argyridis I,Erwin KN,Pegram K,Kneifel M,Rosenberg PB,Matak P,Xie L,Grandl J,Davis EE,Katsanis N,Liu C,Benner EJ

更新日期：2017-10-10 00:00:00

abstract：:Cyclic-di-GMP (c-di-GMP) is a bacterial second messenger that transduces internal and external signals and regulates bacterial motility and biofilm formation. Some organisms encode more than 100 c-di-GMP-modulating enzymes, but only for a few has a signal been defined that modulates their activity. We developed and ap...

journal_title：Science signaling

authors： Mills E,Petersen E,Kulasekara BR,Miller SI

更新日期：2015-06-09 00:00:00

abstract：:In this issue of Science Signaling, Lu et al reveal a role for Parkin-mediated mitophagy in beige-to-white adipocyte transition. In the absence of Parkin, mitochondria in thermogenic beige adipocytes are preserved even after the elimination of cold mimetic stimuli-in contrast to their typical elimination during the wh...

journal_title：Science signaling

authors： Sarraf SA,Youle RJ

更新日期：2018-04-24 00:00:00

abstract：:Cytotoxic lymphocytes share the presence of the activating receptor NK receptor group 2, member D (NKG2D) and the signaling-competent adaptor DNAX-activating protein 10 (DAP10), which together play an important role in antitumor immune surveillance. Ligand stimulation induces the internalization of NKG2D-DAP10 complex...

journal_title：Science signaling

authors： Quatrini L,Molfetta R,Zitti B,Peruzzi G,Fionda C,Capuano C,Galandrini R,Cippitelli M,Santoni A,Paolini R

更新日期：2015-10-27 00:00:00