Probing the mutational landscape of regulators of G protein signaling proteins in cancer.

abstract：:T helper (T(H)) cells integrate biochemical cues present in the tissue microenvironment and produce cytokines that orchestrate immune responses. Previous discoveries have revealed a qualitative understanding of how T(H) cells process this biochemical information; however, the lack of methods to quantify how well these...

journal_title：Science signaling

authors： Klinke DJ 2nd,Cheng N,Chambers E

更新日期：2012-04-17 00:00:00

abstract：:Vitamin D receptor represses basal autophagy in breast tissue, which is derepressed by vitamin D, slowing cancer progression. ...

journal_title：Science signaling

authors： Mushegian AA

更新日期：2017-03-21 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：: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：:Extracellular hyperosmolarity, or osmotic stress, generally caused by differences in salt and macromolecule concentrations across the plasma membrane, occurs in lymphoid organs and at inflammatory sites. The response of immune cells to osmotic stress is regulated by nuclear factor of activated T cells 5 (NFAT5), a tra...

journal_title：Science signaling

authors： Kino T,Takatori H,Manoli I,Wang Y,Tiulpakov A,Blackman MR,Su YA,Chrousos GP,DeCherney AH,Segars JH

更新日期：2009-02-10 00:00:00

abstract：:One reported function of the tumor suppressor p19(Arf) is to stabilize p53, providing a critical checkpoint in the response to oncogenic insults. Acute loss of Pten leads to an increase in the abundance of p19(Arf), p53, and p21 proteins as part of a fail-safe senescence response. Here, we report that loss of p19(Arf)...

journal_title：Science signaling

authors： Chen Z,Carracedo A,Lin HK,Koutcher JA,Behrendt N,Egia A,Alimonti A,Carver BS,Gerald W,Teruya-Feldstein J,Loda M,Pandolfi PP

更新日期：2009-08-18 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：:Inositol pyrophosphates are highly energetic inositol polyphosphate molecules present in organisms from slime molds and yeast to mammals. Distinct classes of enzymes generate different forms of inositol pyrophosphates. The biosynthesis of these substances principally involves phosphorylation of inositol hexakisphospha...

journal_title：Science signaling

authors： Chakraborty A,Kim S,Snyder SH

更新日期：2011-08-23 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：: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 mechanisms of context-specific differences in signal transduction, such as those that occur among different cell types, are not fully understood. One possibility is that differences in the abundance of proteins change signaling outputs because these proteins compete for binding to hub proteins at critical network ...

journal_title：Science signaling

authors： Kiel C,Verschueren E,Yang JS,Serrano L

更新日期：2013-12-17 00:00:00

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：: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：: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：: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：:In Drosophila, recognition of microbe-specific molecules (such as bacterial peptidoglycans) activates serine protease cascades that converge to activate the Toll pathway. Recent data show that the serine protease Grass, which is activated downstream of pattern recognition receptors and was initially thought to be a co...

journal_title：Science signaling

authors： Ashok Y

更新日期：2009-01-06 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：: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：: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：: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 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：:Frizzleds (FZDs) are a group of seven transmembrane-spanning (7TM) receptors that belong to class F of the G protein-coupled receptor (GPCR) superfamily. FZDs bind WNT proteins to stimulate diverse signaling cascades involved in embryonic development, stem cell regulation, and adult tissue homeostasis. Frizzled 5 (FZD...

journal_title：Science signaling

authors： Wright SC,Cañizal MCA,Benkel T,Simon K,Le Gouill C,Matricon P,Namkung Y,Lukasheva V,König GM,Laporte SA,Carlsson J,Kostenis E,Bouvier M,Schulte G,Hoffmann C

更新日期：2018-12-04 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：: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：: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：:Recent studies have identified adaptations of intracellular signaling pathways and target genes that could contribute or modulate the action of antidepressant drugs, as well as exercise-mediated antidepressant responses. Understanding these adaptations, particularly those changes that are common to diverse antidepress...

journal_title：Science signaling

authors： Malberg JE,Monteggia LM

更新日期：2008-05-06 00:00:00

abstract：:A system-wide analysis of cell signaling requires detecting and quantifying many different proteins and their posttranslational modification states in the same cellular sample. Here, we present Protocols for two miniaturized, array-based methods, one of which provides detailed information on a central signaling protei...

journal_title：Science signaling

authors： Luckert K,Gujral TS,Chan M,Sevecka M,Joos TO,Sorger PK,Macbeath G,Pötz O

更新日期：2012-01-10 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：: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：: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