Integrative analysis of kinase networks in TRAIL-induced apoptosis provides a source of potential targets for combination therapy.

abstract：:The mTORC1 [mammalian (or mechanistic) target of rapamycin complex 1] inhibitor rapamycin is a potent inhibitor of T and B lymphocyte growth and proliferation. In this issue of Science Signaling, So et al found that the isoform of 4E-BP (4E-BP2) in lymphocytes that regulates messenger RNA translation is more sensitive...

journal_title：Science signaling

authors： Abraham RT

更新日期：2016-05-31 00:00:00

abstract：:Oxytocin and vasopressin mediate various physiological functions that are important for osmoregulation, reproduction, cardiovascular function, social behavior, memory, and learning through four G protein-coupled receptors that are also implicated in high-profile disorders. Targeting these receptors is challenging beca...

journal_title：Science signaling

authors： Muttenthaler M,Andersson Å,Vetter I,Menon R,Busnelli M,Ragnarsson L,Bergmayr C,Arrowsmith S,Deuis JR,Chiu HS,Palpant NJ,O'Brien M,Smith TJ,Wray S,Neumann ID,Gruber CW,Lewis RJ,Alewood PF

更新日期：2017-12-05 00:00:00

abstract：:Mechanical loading of the skeleton is essential for the development, growth, and maintenance of strong, weight-bearing bones. Bone strength is plastic and can be modulated in adults, as illustrated by the increased bone mass in the playing arms of athletes as compared with their nonplaying arms. Our studies have shown...

journal_title：Science signaling

authors： Turner CH,Warden SJ,Bellido T,Plotkin LI,Kumar N,Jasiuk I,Danzig J,Robling AG

更新日期：2009-04-28 00:00:00

abstract：:Calcium/calmodulin-dependent protein kinase II (CaMKII) plays a central role in Ca2+ signaling throughout the body. In the hippocampus, CaMKII is required for learning and memory. Vertebrate genomes encode four CaMKII homologs: CaMKIIα, CaMKIIβ, CaMKIIγ, and CaMKIIδ. All CaMKIIs consist of a kinase domain, a regulator...

journal_title：Science signaling

authors： Sloutsky R,Dziedzic N,Dunn MJ,Bates RM,Torres-Ocampo AP,Boopathy S,Page B,Weeks JG,Chao LH,Stratton MM

更新日期：2020-07-21 00:00:00

abstract：:Natural killer group 2D (NKG2D), an activating receptor on natural killer (NK) cells and a subset of T cells, recognizes stress-inducible proteins, including MICA and ULBP2, which are present on infected or transformed cells. Whether each NKG2D ligand (NKG2DL) has a distinct biological role is not clear. Using superre...

journal_title：Science signaling

authors： Bálint Š,Lopes FB,Davis DM

更新日期：2018-04-10 00:00:00

abstract：:Spontaneous neural differentiation of embryonic stem cells is induced by Noggin-mediated inhibition of bone morphogenetic protein 4 (BMP4) signaling. RhoA is a guanosine triphosphatase (GTPase) that regulates cytoskeletal dynamics and gene expression, both of which control stem cell fate. We found that disruption of S...

journal_title：Science signaling

authors： Yang J,Wu C,Stefanescu I,Jakobsson L,Chervoneva I,Horowitz A

更新日期：2016-07-26 00:00:00

abstract：:When we are frightened, our hearts beat more rapidly and forcefully so we can fight more intensely or run away faster. This fight-or-flight response is triggered by the release of norepinephrine from neurons of the sympathetic nervous system. Norepinephrine activates the classic β-adrenergic receptor-heterotrimeric G(...

journal_title：Science signaling

authors： Hell JW

更新日期：2010-09-28 00:00:00

abstract：:Multicellular organisms rely on complex, fine-tuned protein networks to respond to environmental changes. We used in vitro evolution to explore the role of domain mutation and expansion in the evolution of network complexity. Using random mutagenesis to facilitate family expansion, we asked how versatile and robust th...

journal_title：Science signaling

authors： Ernst A,Sazinsky SL,Hui S,Currell B,Dharsee M,Seshagiri S,Bader GD,Sidhu SS

更新日期：2009-09-08 00:00:00

abstract：:The diacylglycerol kinases (DGKs) attenuate diacylglycerol (DAG)-mediated signals by catalyzing the conversion of DAG to phosphatidic acid. In T lymphocytes, the antigen-stimulated generation of DAG links signal strength to the intensity and duration of signaling by the Ras-extracellular signal-regulated kinase (ERK) ...

journal_title：Science signaling

authors： Mérida I,Andrada E,Gharbi SI,Ávila-Flores A

更新日期：2015-04-28 00:00:00

abstract：:Signaling pathways control cell fate decisions that ultimately determine the behavior of cancer cells. Therefore, the dynamics of pathway activity may contain prognostically relevant information different from that contained in the static nature of other types of biomarkers. To investigate this hypothesis, we characte...

journal_title：Science signaling

authors： Fey D,Halasz M,Dreidax D,Kennedy SP,Hastings JF,Rauch N,Munoz AG,Pilkington R,Fischer M,Westermann F,Kolch W,Kholodenko BN,Croucher DR

更新日期：2015-12-22 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：:Plants and animals produce reactive oxygen species (ROS) in response to infection. In plants, ROS not only activate defense responses and promote cell death to limit the spread of pathogens but also restrict the amount of cell death in response to pathogen recognition. Plants also use hormones, such as salicylic acid,...

journal_title：Science signaling

authors： Siddique S,Matera C,Radakovic ZS,Hasan MS,Gutbrod P,Rozanska E,Sobczak M,Torres MA,Grundler FM

更新日期：2014-04-08 00:00:00

abstract：:A challenge for biomedical research is the development of pharmaceuticals that appropriately target disease mechanisms. Natural products can be a rich source of bioactive chemicals for medicinal applications but can act through unknown mechanisms and can be difficult to produce or obtain. To address these challenges, ...

journal_title：Science signaling

authors： Potts MB,Kim HS,Fisher KW,Hu Y,Carrasco YP,Bulut GB,Ou YH,Herrera-Herrera ML,Cubillos F,Mendiratta S,Xiao G,Hofree M,Ideker T,Xie Y,Huang LJ,Lewis RE,MacMillan JB,White MA

更新日期：2013-10-15 00:00:00

abstract：:Oxygen sensing by the carotid body is essential in vertebrates to adapt to reduced arterial oxygen tension. In this issue of Science Signaling, Yuan et al. report an intricate signaling system to transduce a physical parameter--oxygen tension--into a biological cellular signal (neural discharge) through changes in the...

journal_title：Science signaling

authors： Fandrey J

更新日期：2015-04-21 00:00:00

abstract：:The prevalence, presentation, and progression of Alzheimer's disease (AD) differ between men and women, although β-amyloid (Aβ) deposition is a pathological hallmark of AD in both sexes. Aβ-induced activation of the neuronal glutamate receptor mGluR5 is linked to AD progression. However, we found that mGluR5 exhibits ...

journal_title：Science signaling

authors： Abd-Elrahman KS,Albaker A,de Souza JM,Ribeiro FM,Schlossmacher MG,Tiberi M,Hamilton A,Ferguson SSG

更新日期：2020-12-15 00:00:00

abstract：:Insight into the signaling pathways that regulate de novo lipogenesis may lead to new treatments for hepatic steatosis. ...

journal_title：Science signaling

authors： Wong W

更新日期：2017-02-21 00:00:00

abstract：:The extracellular Ca(2+)-sensing receptor (CaSR) plays a nonredundant role in the functions of the parathyroid gland (PTG) and the kidney. Severe hyperparathyroidism, premature death, and incomplete gene excision in Casr(-/-) mice have precluded the assessment of CaSR function in other tissues. We generated mice with ...

journal_title：Science signaling

authors： Chang W,Tu C,Chen TH,Bikle D,Shoback D

更新日期：2008-09-02 00:00:00

abstract：:Obesity or a high-fat diet represses the endoribonuclease activity of inositol-requiring enzyme 1α (IRE1α), a transducer of the unfolded protein response (UPR) in cells under endoplasmic reticulum (ER) stress. An impaired UPR is associated with hepatic steatosis and nonalcoholic fatty liver disease (NAFLD), which is c...

journal_title：Science signaling

authors： Wang JM,Qiu Y,Yang Z,Kim H,Qian Q,Sun Q,Zhang C,Yin L,Fang D,Back SH,Kaufman RJ,Yang L,Zhang K

更新日期：2018-05-15 00:00:00

abstract：:This two-issue series focuses on how understanding how signaling pathways are altered in cancer cells can enable researchers to develop more effective therapies. Cancer is a pleiotropic disease. Tumor cells change over time and, even within a specific tumor, cells may have different mutations and dependencies on diffe...

journal_title：Science signaling

authors： Gough NR

更新日期：2013-03-26 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：:The differentiation of fibroblasts into a transient population of highly activated, extracellular matrix (ECM)-producing myofibroblasts at sites of tissue injury is critical for normal tissue repair. Excessive myofibroblast accumulation and persistence, often as a result of a failure to undergo apoptosis when tissue r...

journal_title：Science signaling

authors： Selvarajah B,Azuelos I,Platé M,Guillotin D,Forty EJ,Contento G,Woodcock HV,Redding M,Taylor A,Brunori G,Durrenberger PF,Ronzoni R,Blanchard AD,Mercer PF,Anastasiou D,Chambers RC

更新日期：2019-05-21 00:00:00

abstract：:Progression through mitosis depends on a large number of protein complexes that regulate the major structural and physiological changes necessary for faithful chromosome segregation. Most, if not all, of the mitotic processes are regulated by a set of mitotic protein kinases that control protein activity by phosphoryl...

journal_title：Science signaling

authors： Hegemann B,Hutchins JR,Hudecz O,Novatchkova M,Rameseder J,Sykora MM,Liu S,Mazanek M,Lénárt P,Hériché JK,Poser I,Kraut N,Hyman AA,Yaffe MB,Mechtler K,Peters JM

更新日期：2011-11-08 00:00:00

abstract：:l-Glutamate is the main excitatory neurotransmitter in the brain, with postsynaptic responses to its release predominantly mediated by AMPA-type glutamate receptors (AMPARs). A critical component of synaptic plasticity involves changes in the number of responding postsynaptic receptors, which are dynamically recruited...

journal_title：Science signaling

authors： Buonarati OR,Hammes EA,Watson JF,Greger IH,Hell JW

更新日期：2019-01-01 00:00:00

abstract：:Regulatory T (T(reg)) cells are a unique CD4(+) T cell lineage that plays a crucial role in the maintenance of immunological tolerance. The Forkhead box transcription factor Foxp3 is critically involved in T(reg) cell development and responsible for determining the suppressive function of these cells. The majority of ...

journal_title：Science signaling

authors： Toker A,Huehn J

更新日期：2011-02-01 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 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：: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 prevailing view has been that N-terminally truncated p53 family isoforms (ΔNp53, ΔNp63, and DNp73) predominantly counteract cell cycle arrest and apoptosis. Recent progress in the field extend these well-known functions and place these isoforms in the center of a comprehensive regulatory network controlling major ...

journal_title：Science signaling

authors： Engelmann D,Pützer BM

更新日期：2014-09-30 00:00:00

abstract：:The aggregation of α-synuclein (αSyn) is considered a key pathophysiological feature of certain neurodegenerative disorders, collectively termed synucleinopathies. Given that a prion-like, cell-to-cell transfer of misfolded αSyn has been recognized in the spreading of αSyn pathology in synucleinopathies, we investigat...

journal_title：Science signaling

authors： Harischandra DS,Rokad D,Neal ML,Ghaisas S,Manne S,Sarkar S,Panicker N,Zenitsky G,Jin H,Lewis M,Huang X,Anantharam V,Kanthasamy A,Kanthasamy AG

更新日期：2019-03-12 00:00:00

abstract：:The activation of T cells requires the guanine nucleotide exchange factor VAV1. Using mice in which a tag for affinity purification was attached to endogenous VAV1 molecules, we analyzed by quantitative mass spectrometry the signaling complex that assembles around activated VAV1. Fifty VAV1-binding partners were ident...

journal_title：Science signaling

authors： Gaud G,Roncagalli R,Chaoui K,Bernard I,Familiades J,Colacios C,Kassem S,Monsarrat B,Burlet-Schiltz O,de Peredo AG,Malissen B,Saoudi A

更新日期：2018-07-10 00:00:00