Dysregulation of microRNA biogenesis and gene silencing in cancer.

abstract：:The CXC chemokine CXCL12 mediates the chemoattraction of T cells and enhances the stimulation of T cells through the T cell receptor (TCR). The adaptor SLP-76 [Src homology 2 (SH2) domain-containing leukocyte protein of 76 kD] has two key tyrosine residues, Tyr(113) and Tyr(128), that mediate signaling downstream of t...

journal_title：Science signaling

authors： Smith X,Schneider H,Köhler K,Liu H,Lu Y,Rudd CE

更新日期：2013-07-30 00:00:00

abstract：:We previously developed a web tool, Transcriptomine, to explore expression profiling data sets involving small-molecule or genetic manipulations of nuclear receptor signaling pathways. We describe advances in biocuration, query interface design, and data visualization that enhance the discovery of uncharacterized biol...

journal_title：Science signaling

authors： Becnel LB,Ochsner SA,Darlington YF,McOwiti A,Kankanamge WH,Dehart M,Naumov A,McKenna NJ

更新日期：2017-04-25 00:00:00

abstract：:The proteasome plays a pivotal role in the cellular response to oxidative stress. Here, we used biochemical and mass spectrometric methods to investigate structural changes in the 26S proteasomes from yeast and mammalian cells exposed to hydrogen peroxide (H₂O₂). Oxidative stress induced the dissociation of the 20S co...

journal_title：Science signaling

authors： Wang X,Yen J,Kaiser P,Huang L

更新日期：2010-12-07 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：:Genetically encoded fluorescent sensors enable cell-specific measurements of ions and small molecules in real time. Cyclic adenosine monophosphate (cAMP) is one of the most important signaling molecules in virtually all cell types and organisms. We describe cAMPr, a new single-wavelength cAMP sensor. We developed cAMP...

journal_title：Science signaling

authors： Hackley CR,Mazzoni EO,Blau J

更新日期：2018-03-06 00:00:00

abstract：:Multiple sclerosis (MS) is a human disease that results from autoimmune T cells targeting myelin protein that is expressed within the central nervous system. In MS, the number of FoxP3-expressing regulatory T cells (Tregs) is reduced, which facilitates the activation of autoreactive T cells. Because aspirin (acetylsal...

journal_title：Science signaling

authors： Mondal S,Jana M,Dasarathi S,Roy A,Pahan K

更新日期：2018-11-27 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：:Regulatory factor X (Rfx) homologs regulate the transcription of genes necessary for ciliogenesis in invertebrates and vertebrates. Primary cilia are necessary for Hedgehog signaling and regulation of the activity of the transcriptional regulators known as Gli proteins, which are targets of Hedgehog signaling. Here, w...

journal_title：Science signaling

authors： Ashique AM,Choe Y,Karlen M,May SR,Phamluong K,Solloway MJ,Ericson J,Peterson AS

更新日期：2009-11-03 00:00:00

abstract：:Signaling by the transforming growth factor-β (TGF-β) receptors I and II (TβRI/II) and the primary cilia-localized sonic hedgehog (Shh) pathway promote cell migration and, consequently, tumor metastasis. In contrast, the sphingolipid ceramide inhibits cell proliferation and tumor metastasis. We investigated whether ce...

journal_title：Science signaling

authors： Gencer S,Oleinik N,Kim J,Panneer Selvam S,De Palma R,Dany M,Nganga R,Thomas RJ,Senkal CE,Howe PH,Ogretmen B

更新日期：2017-10-24 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 deubiquitylating enzyme OTUB1 is present in all tissues and targets many substrates, in both the cytosol and nucleus. We found that casein kinase 2 (CK2) phosphorylated OTUB1 at Ser(16) to promote its nuclear accumulation in cells. Pharmacological inhibition or genetic ablation of CK2 blocked the phosphorylation o...

journal_title：Science signaling

authors： Herhaus L,Perez-Oliva AB,Cozza G,Gourlay R,Weidlich S,Campbell DG,Pinna LA,Sapkota GP

更新日期：2015-04-14 00:00:00

abstract：:The cytoplasmic phosphatase PTPN22 (protein tyrosine phosphatase nonreceptor type 22) plays a key role in regulating lymphocyte homeostasis, which ensures that the total number of lymphocytes in the periphery remains relatively constant. Mutations in PTPN22 confer an increased risk of developing autoimmune diseases; h...

journal_title：Science signaling

authors： Brownlie RJ,Miosge LA,Vassilakos D,Svensson LM,Cope A,Zamoyska R

更新日期：2012-11-27 00:00:00

abstract：:Insulin receptor substrate 2 (IRS2) is an adaptor protein that becomes tyrosine-phosphorylated in response to the cytokines interleukin-4 (IL-4) and IL-13, which results in activation of the phosphoinositide 3-kinase (PI3K)-Akt pathway. IL-4 and IL-13 contribute to allergic lung inflammation. To examine the role of IR...

journal_title：Science signaling

authors： Dasgupta P,Dorsey NJ,Li J,Qi X,Smith EP,Yamaji-Kegan K,Keegan AD

更新日期：2016-06-21 00:00:00

abstract：:A major endpoint of the canonical Wnt signaling pathway is a change in the transcription of target genes. The transcription factors lymphoid enhancer factor (LEF) and T cell factor (TCF) serve as the main gatekeepers of these changes by selecting genes to be targeted by the transcriptional coregulator beta-catenin and...

journal_title：Science signaling

authors： Hoverter NP,Waterman ML

更新日期：2008-09-30 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：:Nominations for this year's signaling breakthroughs spanned physiology, therapeutics and drug development, neuroscience, and plant signaling. Among the most exciting advances in mammalian biology were therapeutic applications of research that are overturning the conventional boundaries of signaling pathways,unexpected...

journal_title：Science signaling

authors： Adler EM

更新日期：2010-01-05 00:00:00

abstract：:Ligand binding to certain heterotrimeric guanine nucleotide-binding protein (G protein)-coupled receptors (GPCRs) stimulates the rapid synthesis of cyclic adenosine monophosphate (cAMP) through the G protein α(s) subunit, which activates adenylyl cyclase (AC). We found that the transmembrane receptor low-density lipop...

journal_title：Science signaling

authors： Wan M,Li J,Herbst K,Zhang J,Yu B,Wu X,Qiu T,Lei W,Lindvall C,Williams BO,Ma H,Zhang F,Cao X

更新日期：2011-03-15 00:00:00

abstract：:Activation of Ca2+-sensitive, large-conductance potassium (BK) channels in vascular smooth muscle cells (VSMCs) by local, ryanodine receptor-mediated Ca2+ signals (Ca2+ sparks) acts as a brake on pressure-induced (myogenic) vasoconstriction-a fundamental mechanism that regulates blood flow in small resistance arteries...

journal_title：Science signaling

authors： Khavandi K,Baylie RA,Sugden SA,Ahmed M,Csato V,Eaton P,Hill-Eubanks DC,Bonev AD,Nelson MT,Greenstein AS

更新日期：2016-10-11 00:00:00

abstract：:MicroRNAs (miRNAs), key posttranscriptional regulators of many biological processes, have been implicated in many diseases, including cancer. In a recent paper, Avraham and colleagues take a systems biology approach to determine whether and how miRNAs are involved in the regulation of oncogenic signaling networks down...

journal_title：Science signaling

authors： Herschkowitz JI,Fu X

更新日期：2011-07-26 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：:Defects in the biogenesis of or transport through primary cilia affect Hedgehog protein signaling, and many Hedgehog pathway components traffic through or accumulate in cilia. The Hedgehog receptor Patched negatively regulates the activity and ciliary accumulation of Smoothened, a seven-transmembrane protein that is e...

journal_title：Science signaling

authors： Kim J,Hsia EY,Brigui A,Plessis A,Beachy PA,Zheng X

更新日期：2015-06-02 00:00:00

abstract：:Type 1 diabetes mellitus (T1DM) is associated with chronic systemic inflammation and enhanced susceptibility to systemic bacterial infection (sepsis). We hypothesized that low insulin concentrations in T1DM trigger the enzyme 5-lipoxygenase (5-LO) to produce the lipid mediator leukotriene B4 (LTB4), which triggers sys...

journal_title：Science signaling

authors： Filgueiras LR,Brandt SL,Wang S,Wang Z,Morris DL,Evans-Molina C,Mirmira RG,Jancar S,Serezani CH

更新日期：2015-01-27 00:00:00

abstract：:Store-operated Ca2+ entry (SOCE) is critical for salivary gland fluid secretion. We report that radiation treatment caused persistent salivary gland dysfunction by activating a TRPM2-dependent mitochondrial pathway, leading to caspase-3-mediated cleavage of stromal interaction molecule 1 (STIM1) and loss of SOCE. Afte...

journal_title：Science signaling

authors： Liu X,Gong B,de Souza LB,Ong HL,Subedi KP,Cheng KT,Swaim W,Zheng C,Mori Y,Ambudkar IS

更新日期：2017-06-06 00:00:00

abstract：:Tools for conducting high-throughput kinome analysis do not exist for many species. For example, two commonly used techniques for monitoring phosphorylation events are phosphorylation-specific antibodies and peptide arrays. The majority of phosphorylation-specific antibodies are for human or mouse targets, and the con...

journal_title：Science signaling

authors： Jalal S,Arsenault R,Potter AA,Babiuk LA,Griebel PJ,Napper S

更新日期：2009-01-20 00:00:00

abstract：:The LKB1 serine-threonine kinase is a tumor suppressor that is inactivated in a large number of sporadic human lung non-small cell carcinomas (NSCLCs) and cervical cancers. Genetic deletion of LKB1 in various mouse tissues results in tumorigenesis, and loss of LKB1 increases metastasis in a mouse model of NSCLC. LKB1 ...

journal_title：Science signaling

authors： Shaw RJ

更新日期：2009-09-01 00:00:00

abstract：:Dimers of conventional transforming growth factor-β (TGF-β) and bone morphogenetic protein (BMP) ligands are composed of two 100- to 140-amino acid peptides that are produced through the proteolytic processing of a proprotein precursor by proconvertases, such as furin. We report the identification of an evolutionarily...

journal_title：Science signaling

authors： Akiyama T,Marqués G,Wharton KA

更新日期：2012-04-03 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：: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：:An often-asked question is, Why are there so many different transporters in a cell to take up a particular substrate? At least part of the answer comes from work on the possible competitive advantage of dual-transporter systems. In such systems, low-affinity transporters function when a nutrient is plentiful in the en...

journal_title：Science signaling

authors： Eide DJ

更新日期：2012-02-07 00:00:00

abstract：:The hypoxia inducible factors (HIFs) and CCAAT/enhancer binding protein alpha (C/EBP alpha) are transcription factors that mediate adaptive responses to hypoxia and control aspects of energy metabolism, respectively. New evidence suggests that when HIF-1 alpha and C/EBP alpha interact, they bring about reciprocal func...

journal_title：Science signaling

authors： Janardhan HP

更新日期：2008-10-28 00:00:00