Wingless promotes proliferative growth in a gradient-independent manner.

abstract：:Neutrophil extracellular trap (NET) formation can generate short-term, functional anucleate cytoplasts and trigger loss of cell viability. We demonstrated that the necroptotic cell death effector mixed lineage kinase domain-like (MLKL) translocated from the cytoplasm to the plasma membrane and stimulated downstream NA...

journal_title：Science signaling

authors： D'Cruz AA,Speir M,Bliss-Moreau M,Dietrich S,Wang S,Chen AA,Gavillet M,Al-Obeidi A,Lawlor KE,Vince JE,Kelliher MA,Hakem R,Pasparakis M,Williams DA,Ericsson M,Croker BA

更新日期：2018-09-04 00:00:00

abstract：:The V600E mutation in the kinase BRAF is frequently detected in melanomas and results in constitutive activation of BRAF, which then promotes cell proliferation by the mitogen-activated protein kinase signaling pathway. Although the BRAFV600E kinase inhibitor vemurafenib has remarkable antitumor activity in patients w...

journal_title：Science signaling

authors： Beck D,Niessner H,Smalley KS,Flaherty K,Paraiso KH,Busch C,Sinnberg T,Vasseur S,Iovanna JL,Drießen S,Stork B,Wesselborg S,Schaller M,Biedermann T,Bauer J,Lasithiotakis K,Weide B,Eberle J,Schittek B,Schadendorf D,G

更新日期：2013-01-29 00:00:00

abstract：:In a mouse model of Parkinson's disease, new evidence shows that l-DOPA, which is used to treat the symptoms of the disease but also causes dyskinesia, results in a persistent activation of the protein kinase mTOR (mammalian target of rapamycin) in a subset of striatal medium spiny neurons. Moreover, blockade of a spe...

journal_title：Science signaling

authors： Klann E

更新日期：2009-07-21 00:00:00

abstract：:The K+/Cl- cotransporter KCC2 is a molecular switch between excitatory and inhibitory effects of GABAergic inputs into neurons. In a pair of exciting studies, Watanabe et al. and Pisella et al. elucidate the role of KCC2 dephosphorylation in this process and reveal its consequences for neurodevelopment and nervous sys...

journal_title：Science signaling

authors： Zamponi GW

更新日期：2019-10-15 00:00:00

abstract：:Degrons are the elements that are used by E3 ubiquitin ligases to target proteins for degradation. Most degrons are short linear motifs embedded within the sequences of modular proteins. As regulatory sites for protein abundance, they are important for many different cellular processes, such as progression through the...

journal_title：Science signaling

authors： Mészáros B,Kumar M,Gibson TJ,Uyar B,Dosztányi Z

更新日期：2017-03-14 00:00:00

abstract：:The hexosamine biosynthetic pathway, whose end product is UDP-N acetylglucosamine (UDP-GlcNAc), lies at the base of cellular glycosylation pathways, including glycosylation of lipids, formation of heparin sulfated proteoglycans, and N- and O-linked glycosylation of proteins. Forward genetic studies in Drosophila have ...

journal_title：Science signaling

authors： Ghabrial AS

更新日期：2012-01-17 00:00:00

abstract：:Cancer-associated pain is debilitating. Understanding the mechanisms that cause it can inform drug development that may improve quality of life in patients. Here, we found that the reduced abundance of potassium channels called TRESK in dorsal root ganglion (DRG) neurons sensitized nociceptive sensory neurons and canc...

journal_title：Science signaling

authors： Yang Y,Li S,Jin ZR,Jing HB,Zhao HY,Liu BH,Liang YJ,Liu LY,Cai J,Wan Y,Xing GG

更新日期：2018-10-16 00:00:00

abstract：:Secreted IgD concentration depends on the presence of microbiota. ...

journal_title：Science signaling

authors： Mushegian AA

更新日期：2017-02-21 00:00:00

abstract：:Secretory cells, such as pancreatic beta cells, face the challenge of increasing protein synthesis severalfold during acute or chronic stimulation. This poses a burden on the endoplasmic reticulum (ER), the organelle where proinsulin synthesis and folding takes place. Thus, beta cells use various adaptive mechanisms t...

journal_title：Science signaling

authors： Eizirik DL,Cnop M

更新日期：2010-02-23 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：:Compared with the luminal subtype, the basal-like subtype of breast cancer has an aggressive clinical behavior, but the reasons for this difference between the two subtypes are poorly understood. We identified microRNAs (miRNAs) miR-221 and miR-222 (miR-221/222) as basal-like subtype-specific miRNAs that decrease expr...

journal_title：Science signaling

authors： Stinson S,Lackner MR,Adai AT,Yu N,Kim HJ,O'Brien C,Spoerke J,Jhunjhunwala S,Boyd Z,Januario T,Newman RJ,Yue P,Bourgon R,Modrusan Z,Stern HM,Warming S,de Sauvage FJ,Amler L,Yeh RF,Dornan D

更新日期：2011-08-09 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：:Vitamin E is a fat-soluble vitamin with antioxidant properties. Tocopherols are the predominant form of vitamin E found in the diet and in supplements and have garnered interest for their potential cancer therapeutic and preventive effects, such as the dephosphorylation of Akt, a serine/threonine kinase with a pivotal...

journal_title：Science signaling

authors： Huang PH,Chuang HC,Chou CC,Wang H,Lee SL,Yang HC,Chiu HC,Kapuriya N,Wang D,Kulp SK,Chen CS

更新日期：2013-03-19 00:00:00

abstract：:The C-terminal guanine nucleotide exchange factor (GEF) module of Trio (TrioC) transfers signals from the Gαq/11 subfamily of heterotrimeric G proteins to the small guanosine triphosphatase (GTPase) RhoA, enabling Gαq/11-coupled G protein-coupled receptors (GPCRs) to control downstream events, such as cell motility an...

journal_title：Science signaling

authors： Bandekar SJ,Arang N,Tully ES,Tang BA,Barton BL,Li S,Gutkind JS,Tesmer JJG

更新日期：2019-02-19 00:00:00

abstract：:Cross-linking of proteins by mammalian transglutaminases (TGs) plays important roles in physiological phenomena such as blood coagulation and skin formation. We show that Drosophila TG suppressed innate immune signaling in the gut. RNA interference (RNAi) directed against TG reduced the life span of flies reared under...

journal_title：Science signaling

authors： Shibata T,Sekihara S,Fujikawa T,Miyaji R,Maki K,Ishihara T,Koshiba T,Kawabata S

更新日期：2013-07-23 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：:This year's signaling breakthroughs highlight insights into the pathogenesis or treatment of cancer, malaria, and neurodegenerative disorders; reveal molecular insights into cell death; and identify signals that could be leveraged to prevent plant parasitism or engineer bacteria as microbial fuel cells. ...

journal_title：Science signaling

authors： Adler EM

更新日期：2016-01-05 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：:This two-part lecture introduces students to the scientific computing language MATLAB. Prior computer programming experience is not required. The lectures present basic concepts of computer programming logic that tend to cause difficulties for beginners in addition to concepts that relate specifically to the MATLAB la...

journal_title：Science signaling

authors： Sobie EA

更新日期：2011-09-13 00:00:00

abstract：:New therapeutic approaches for chronic inflammatory diseases such as inflammatory bowel disease, rheumatoid arthritis, and psoriasis are needed because current treatments are often suboptimal in terms of both efficacy and the risks of serious adverse events. Inhibitor of apoptosis proteins (IAPs) are E3 ubiquitin liga...

journal_title：Science signaling

authors： Jensen S,Seidelin JB,LaCasse EC,Nielsen OH

更新日期：2020-02-18 00:00:00

abstract：:During T cell activation by antigen-presenting cells (APCs), the diverse spatiotemporal organization of components of T cell signaling pathways modulates the efficiency of activation. Here, we found that loss of the tyrosine kinase interleukin-2 (IL-2)-inducible T cell kinase (Itk) in mice altered the spatiotemporal d...

journal_title：Science signaling

authors： Singleton KL,Gosh M,Dandekar RD,Au-Yeung BB,Ksionda O,Tybulewicz VL,Altman A,Fowell DJ,Wülfing C

更新日期：2011-10-04 00:00:00

abstract：:Manipulating ligand interactions with the activating receptor NKG2D modulates natural killer cell responses. ...

journal_title：Science signaling

authors： Foley JF

更新日期：2017-05-30 00:00:00

abstract：:Fgr is a member of the Src family of nonreceptor tyrosine kinases, which are overexpressed and constitutively active in many human cancers. Fgr expression is restricted to myeloid hematopoietic cells and is markedly increased in a subset of bone marrow samples from patients with acute myeloid leukemia (AML). Here, we ...

journal_title：Science signaling

authors： Shen K,Moroco JA,Patel RK,Shi H,Engen JR,Dorman HR,Smithgall TE

更新日期：2018-10-23 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：:Microglia mediate neuroprotection and neuropathogenesis but have not been directly associated with behavior. As gatekeepers of the brain's immune system, microglia protect the brain from pathogens but also contribute to inflammation, which may negatively affect neurons. A recent study demonstrates a role for Hoxb8-exp...

journal_title：Science signaling

authors： Antony JM

更新日期：2010-11-09 00:00:00

abstract：:Eps15 homology domain (EHD) proteins are conserved adenosine triphosphatases that are involved in membrane remodeling. EHD family members are structurally similar to the guanosine triphosphatase (GTPase) dynamin, and both are essential for the fission step of clathrin-mediated endocytosis. This Journal Club highlights...

journal_title：Science signaling

authors： Ioannou MS,Marat AL

更新日期：2012-04-24 00:00:00

abstract：:Interleukin-10 (IL-10) is an important anti-inflammatory cytokine that is produced primarily by macrophages. We investigated mechanisms by which the timing of IL-10 production was controlled in macrophages and found that cyclin-dependent kinase 5 (CDK5) activity was markedly increased in lipopolysaccharide (LPS)-stimu...

journal_title：Science signaling

authors： Na YR,Jung D,Gu GJ,Jang AR,Suh YH,Seok SH

更新日期：2015-11-24 00:00:00

abstract：:This week, Science Signaling highlights research that uses computational and cell biology approaches to uncover the molecular mechanisms underlying diseases of the central nervous system. In particular, research featured explores the neuronal response to stress due to excess excitatory stimuli, multiple roles for pres...

journal_title：Science signaling

authors： Ferrarelli LK,Gough NR

更新日期：2013-07-09 00:00:00

abstract：:The detection of microbes and initiation of an innate immune response occur through pattern recognition receptors (PRRs), which are critical for the production of inflammatory cytokines and activation of the cellular microbicidal machinery. In particular, the production of reactive oxygen species (ROS) by the NADPH ox...

journal_title：Science signaling

authors： Billings EA,Lee CS,Owen KA,D'Souza RS,Ravichandran KS,Casanova JE

更新日期：2016-02-02 00:00:00

abstract：:Notch signaling is used to choose cell fates in many developmental contexts. New evidence shows that circulating blood cells in Drosophila, in the absence of Notch ligand provided by neighboring cells, activate Notch signaling through stabilization with the hypoxia-inducible factor-α (HIF-α) transcription factor. Alth...

journal_title：Science signaling

authors： Johnson EA

更新日期：2011-07-12 00:00:00