Rapid evolution of functional complexity in a domain family.

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：: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

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：:Deoxyhypusine synthase (DHPS) uses the polyamine spermidine to catalyze the hypusine modification of the mRNA translation factor eIF5A and promotes oncogenesis through poorly defined mechanisms. Because germline deletion of Dhps is embryonically lethal, its role in normal postnatal cellular function in vivo remains un...

journal_title：Science signaling

authors： Levasseur EM,Yamada K,Piñeros AR,Wu W,Syed F,Orr KS,Anderson-Baucum E,Mastracci TL,Maier B,Mosley AL,Liu Y,Bernal-Mizrachi E,Alonso LC,Scott D,Garcia-Ocaña A,Tersey SA,Mirmira RG

更新日期：2019-12-03 00:00:00

abstract：:The activity of the transcription factor hypoxia-inducible factor 1alpha (HIF-1alpha) is increased in response to reduced intracellular oxygen. Enzymes of the protein ubiquitin machinery that signal the destruction or stabilization of HIF-1alpha tightly control this transcriptional response. Here, we show that muscle ...

journal_title：Science signaling

authors： Wong W,Goehring AS,Kapiloff MS,Langeberg LK,Scott JD

更新日期：2008-12-23 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：:Birth defects of the heart and face are common, and most have no known genetic cause, suggesting a role for environmental factors. Maternal fever during the first trimester is an environmental risk factor linked to these defects. Neural crest cells are precursor populations essential to the development of both at-risk...

journal_title：Science signaling

authors： Hutson MR,Keyte AL,Hernández-Morales M,Gibbs E,Kupchinsky ZA,Argyridis I,Erwin KN,Pegram K,Kneifel M,Rosenberg PB,Matak P,Xie L,Grandl J,Davis EE,Katsanis N,Liu C,Benner EJ

更新日期：2017-10-10 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：:Store-operated Ca2+ entry (SOCE) channels are highly selective Ca2+ channels activated by the endoplasmic reticulum (ER) sensors STIM1 and STIM2. Their direct interaction with the pore-forming plasma membrane ORAI proteins (ORAI1, ORAI2, and ORAI3) leads to sustained Ca2+ fluxes that are critical for many cellular fun...

journal_title：Science signaling

authors： Eckstein M,Vaeth M,Aulestia FJ,Costiniti V,Kassam SN,Bromage TG,Pedersen P,Issekutz T,Idaghdour Y,Moursi AM,Feske S,Lacruz RS

更新日期：2019-04-23 00:00:00

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：:In this issue of Science Signaling, Lu et al reveal a role for Parkin-mediated mitophagy in beige-to-white adipocyte transition. In the absence of Parkin, mitochondria in thermogenic beige adipocytes are preserved even after the elimination of cold mimetic stimuli-in contrast to their typical elimination during the wh...

journal_title：Science signaling

authors： Sarraf SA,Youle RJ

更新日期：2018-04-24 00:00:00

abstract：:Ovarian cancer is a complex disease with heterogeneity among the gene expression molecular subtypes (GEMS) between patients. Patients with tumors of a mesenchymal ("Mes") subtype have a poorer prognosis than patients with tumors of an epithelial ("Epi") subtype. We evaluated GEMS of ovarian cancer patients for molecul...

journal_title：Science signaling

authors： Antony J,Tan TZ,Kelly Z,Low J,Choolani M,Recchi C,Gabra H,Thiery JP,Huang RY

更新日期：2016-10-04 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：:Cardiomyocytes contract against a mechanical load during each heartbeat, and excessive mechanical stress leads to heart diseases. Using a cell-in-gel system that imposes an afterload during cardiomyocyte contraction, we found that nitric oxide synthase (NOS) was involved in transducing mechanical load to alter Ca(2+) ...

journal_title：Science signaling

authors： Jian Z,Han H,Zhang T,Puglisi J,Izu LT,Shaw JA,Onofiok E,Erickson JR,Chen YJ,Horvath B,Shimkunas R,Xiao W,Li Y,Pan T,Chan J,Banyasz T,Tardiff JC,Chiamvimonvat N,Bers DM,Lam KS,Chen-Izu Y

更新日期：2014-03-18 00:00:00

abstract：:Parkinson's disease (PD) is a neurodegenerative disorder in which the loss of dopaminergic neurons in the midbrain (mDA neurons) causes progressive loss of motor control and function. Using embryonic and mDA neurons, midbrain tissue from mice, and differentiated human neural stem cells, we investigated the mechanisms ...

journal_title：Science signaling

authors： Zhang D,Yang S,Toledo EM,Gyllborg D,Saltó C,Carlos Villaescusa J,Arenas E

更新日期：2017-08-22 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：: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：:Epigenetic modifications, such as DNA cytosine methylation, contribute to the mechanisms underlying learning and memory by coordinating adaptive gene expression and neuronal plasticity. Transcription-dependent plasticity regulated by DNA methylation includes synaptic plasticity and homeostatic synaptic scaling. Memory...

journal_title：Science signaling

authors： Meadows JP,Guzman-Karlsson MC,Phillips S,Brown JA,Strange SK,Sweatt JD,Hablitz JJ

更新日期：2016-08-23 00:00:00

abstract：:Although multiple steroid ligands of the glucocorticoid, mineralocorticoid, and progestin families bind to and regulate the activity of mineralocorticoid receptors (MRs), the responses to these ligands differ across species. To understand how the different domains of MRs contribute to the ligand-induced activation or ...

journal_title：Science signaling

authors： Katsu Y,Oka K,Baker ME

更新日期：2018-07-03 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：: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：: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 discovery of feedback loops between signaling and gene expression is ushering in new quantitative models of cellular regulation. In a recent issue of Science Signaling, Sung et al. showed how positive feedback downstream of nuclear factor κB (NF-κB) signaling enhances the capacity of macrophages to scale their ant...

journal_title：Science signaling

authors： Tkach KE,Oyler JE,Altan-Bonnet G

更新日期：2014-02-18 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：:The trimeric intracellular cation (TRIC) channels TRIC-A and TRIC-B localize predominantly to the endoplasmic reticulum (ER) and likely support Ca(2+) release from intracellular stores by mediating cationic flux to maintain electrical neutrality. Deletion and point mutations in TRIC-B occur in families with autosomal ...

journal_title：Science signaling

authors： Zhao C,Ichimura A,Qian N,Iida T,Yamazaki D,Noma N,Asagiri M,Yamamoto K,Komazaki S,Sato C,Aoyama F,Sawaguchi A,Kakizawa S,Nishi M,Takeshima H

更新日期：2016-05-17 00:00:00

abstract：:Cellular proliferation, differentiation, and morphogenesis are shaped by multiple signaling cascades, and their dysregulation plays an integral role in cancer progression. Three cascades that contribute to oncogenic potential are those mediated by Wnt proteins and the receptor Frizzled (FZD), growth factor receptor ty...

journal_title：Science signaling

authors： Aznar N,Ear J,Dunkel Y,Sun N,Satterfield K,He F,Kalogriopoulos NA,Lopez-Sanchez I,Ghassemian M,Sahoo D,Kufareva I,Ghosh P

更新日期：2018-02-27 00:00:00

abstract：:Overuse of β2-adrenoceptor agonist bronchodilators evokes receptor desensitization, decreased efficacy, and an increased risk of death in asthma patients. Bronchodilators that do not target β2-adrenoceptors represent a critical unmet need for asthma management. Here, we characterize the utility of osthole, a coumarin ...

journal_title：Science signaling

authors： Wang S,Xie Y,Huo YW,Li Y,Abel PW,Jiang H,Zou X,Jiao HZ,Kuang X,Wolff DW,Huang YG,Casale TB,Panettieri RA Jr,Wei T,Cao Z,Tu Y

更新日期：2020-11-24 00:00:00

abstract：:Signaling proteins evolved diverse interactions to provide specificity for distinct stimuli. Signaling complexity in the G protein (heterotrimeric guanosine triphosphate-binding protein) network was achieved in animals through subunit duplication and incremental evolution. By combining comprehensive and quantitative p...

journal_title：Science signaling

authors： Urano D,Maruta N,Trusov Y,Stoian R,Wu Q,Liang Y,Jaiswal DK,Thung L,Jackson D,Botella JR,Jones AM

更新日期：2016-09-20 00:00:00

abstract：:Mutations in ERBB2, the gene encoding epidermal growth factor receptor (EGFR) family member HER2, are common in and drive the growth of "HER2-negative" (not ERBB2 amplified) tumors but are rare in "HER2-positive" (ERBB2 amplified) breast cancer. We analyzed DNA-sequencing data from HER2-positive patients and used cell...

journal_title：Science signaling

authors： Cocco E,Javier Carmona F,Razavi P,Won HH,Cai Y,Rossi V,Chan C,Cownie J,Soong J,Toska E,Shifman SG,Sarotto I,Savas P,Wick MJ,Papadopoulos KP,Moriarty A,Cutler RE Jr,Avogadri-Connors F,Lalani AS,Bryce RP,Chandarlapa

更新日期：2018-10-09 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