mGluR5 antagonism increases autophagy and prevents disease progression in the zQ175 mouse model of Huntington's disease.

abstract：:The complexity of the signaling network that is initiated by members of the transforming growth factor-beta (TGF-beta) superfamily continues to increase. In addition, Smads, which were originally identified as key transducers of TGF-beta signals, are beginning to emerge as players in other TGF-beta-independent process...

journal_title：Science signaling

authors： Gough NR

更新日期：2008-11-18 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：:Endothelial cell dysfunction, characterized by a diminished response to endothelial cell-dependent vasodilators, is a hallmark of hypertension. TRPV4 channels play a major role in endothelial-dependent vasodilation, a function mediated by local Ca(2+) influx through clusters of functionally coupled TRPV4 channels rath...

journal_title：Science signaling

authors： Sonkusare SK,Dalsgaard T,Bonev AD,Hill-Eubanks DC,Kotlikoff MI,Scott JD,Santana LF,Nelson MT

更新日期：2014-07-08 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：: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 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：: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：:The reciprocal regulation of phosphoprotein phosphatases (PPPs) by protein kinases is essential to cell cycle progression and control, particularly during mitosis for which the role of kinases has been extensively studied. PPPs perform much of the serine/threonine dephosphorylation in eukaryotic cells and achieve subs...

journal_title：Science signaling

authors： Nasa I,Cressey LE,Kruse T,Hertz EPT,Gui J,Graves LM,Nilsson J,Kettenbach AN

更新日期：2020-09-08 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

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：:Chimeric antigen receptors (CARs) link an antigen recognition domain to intracellular signaling domains to redirect T cell specificity and function. T cells expressing CARs with CD28/CD3ζ or 4-1BB/CD3ζ signaling domains are effective at treating refractory B cell malignancies but exhibit differences in effector functi...

journal_title：Science signaling

authors： Salter AI,Ivey RG,Kennedy JJ,Voillet V,Rajan A,Alderman EJ,Voytovich UJ,Lin C,Sommermeyer D,Liu L,Whiteaker JR,Gottardo R,Paulovich AG,Riddell SR

更新日期：2018-08-21 00:00:00

abstract：:Mineralocorticoid receptor (MR) antagonists are effective at treating heart failure. In this issue of Science Signaling, Oakley et al. provide new insight into their cardioprotective actions and highlight the importance of the opposing relationship between the MR and the related glucocorticoid receptor (GR) in the res...

journal_title：Science signaling

authors： Chapman KE

更新日期：2019-04-16 00:00:00

abstract：:Inhibition of protein synthesis by phosphorylation of the alpha subunit of eukaryotic translation initiation factor 2 (eIF2) at Ser(51) occurs as a result of the activation of a family of kinases in response to various forms of stress. Although some consequences of eIF2alpha phosphorylation are cytoprotective, phospho...

journal_title：Science signaling

authors： Mounir Z,Krishnamoorthy JL,Robertson GP,Scheuner D,Kaufman RJ,Georgescu MM,Koromilas AE

更新日期：2009-12-22 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 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

abstract：:The prefibrillar form of soluble amyloid-β (sAβ1-42) impairs synaptic function and is associated with the early phase of Alzheimer's disease (AD). We investigated how sAβ1-42 led to presynaptic defects using a quantum dot-based, single particle-tracking method to monitor synaptic vesicle (SV) trafficking along axons. ...

journal_title：Science signaling

authors： Park D,Na M,Kim JA,Lee U,Cho E,Jang M,Chang S

更新日期：2017-07-11 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：:Pentraxin 3 (PTX3), a member of the long pentraxin subfamily within the family of pentraxins, is a soluble pattern recognition molecule that functions in the innate immune system. Innate immunity affords the infected host protection against sepsis, a potentially life-threatening inflammatory response to infection. Ext...

journal_title：Science signaling

authors： Daigo K,Nakakido M,Ohashi R,Fukuda R,Matsubara K,Minami T,Yamaguchi N,Inoue K,Jiang S,Naito M,Tsumoto K,Hamakubo T

更新日期：2014-09-16 00:00:00

abstract：:K63-linked ubiquitination of Akt is a posttranslational modification that plays a critical role in growth factor-mediated membrane recruitment and activation of Akt. Although E3 ligases involved in growth factor-induced ubiquitination of Akt have been defined, the deubiquitinating enzyme (DUB) that triggers deubiquiti...

journal_title：Science signaling

authors： Yang WL,Jin G,Li CF,Jeong YS,Moten A,Xu D,Feng Z,Chen W,Cai Z,Darnay B,Gu W,Lin HK

更新日期：2013-01-08 00:00:00

abstract：:Both synaptic long-term potentiation (LTP) and long-term depression (LTD) are thought to be critical for memory formation. Dell'Acqua and co-workers now demonstrate that transient postsynaptic incorporation of Ca(2+)-permeable (CP) α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) is required for...

journal_title：Science signaling

authors： Hell JW

更新日期：2016-04-26 00:00:00

abstract：:The cytokine interleukin-22 (IL-22), which is a member of the IL-10 family, is produced exclusively by immune cells and activates signal transducer and activator of transcription 3 (STAT3) in nonimmune cells, such as hepatocytes, keratinocytes, and colonic epithelial cells, to drive various processes central to tissue...

journal_title：Science signaling

authors： Lim C,Hong M,Savan R

更新日期：2016-09-27 00:00:00

abstract：:Phosphatidylinositol 3-kinase-related protein kinase (PIKK) family proteins play essential roles in DNA-based and RNA-based processes, such as the response to DNA damage, messenger RNA (mRNA) quality control, transcription, and translation, where they contribute to the maintenance of genome integrity and accurate gene...

journal_title：Science signaling

authors： Izumi N,Yamashita A,Iwamatsu A,Kurata R,Nakamura H,Saari B,Hirano H,Anderson P,Ohno S

更新日期：2010-04-06 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：: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：: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：:Epithelial cell polarity is linked to the control of tissue growth and tumorigenesis. The tumor suppressor and cell polarity protein lethal-2-giant larvae (Lgl) promotes Hippo signaling and inhibits Notch signaling to restrict tissue growth in Drosophila melanogaster Notch signaling is greater in lgl mutant tissue tha...

journal_title：Science signaling

authors： Portela M,Yang L,Paul S,Li X,Veraksa A,Parsons LM,Richardson HE

更新日期：2018-06-05 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：:Under drought stress, abscisic acid (ABA) triggers closure of leaf cell pores called stomata, which are formed by two specialized cells called guard cells in plant epidermis. Two pathways downstream of ABA stimulate phosphorylation of the S-type anion channels SLAC1 (slow anion channel associated 1) and SLAH3 (SLAC1 h...

journal_title：Science signaling

authors： Maierhofer T,Diekmann M,Offenborn JN,Lind C,Bauer H,Hashimoto K,S Al-Rasheid KA,Luan S,Kudla J,Geiger D,Hedrich R

更新日期：2014-09-09 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：:Vascular endothelial growth factors (VEGFs) regulate blood and lymphatic vessel development through VEGF receptors (VEGFRs). The VEGFR immunoglobulin homology domain 2 (D2) is critical for ligand binding, and D3 provides additional interaction sites. VEGF-B and placenta growth factor (PlGF) bind to VEGFR-1 with high a...

journal_title：Science signaling

authors： Anisimov A,Leppänen VM,Tvorogov D,Zarkada G,Jeltsch M,Holopainen T,Kaijalainen S,Alitalo K

更新日期：2013-07-02 00:00:00