Structure of the C-terminal guanine nucleotide exchange factor module of Trio in an autoinhibited conformation reveals its oncogenic potential.

abstract：:TLR4-stimulated B cell activation is mediated by the tyrosine kinase Syk and depends on the B cell receptor. ...

journal_title：Science signaling

authors： Foley JF

更新日期：2017-05-23 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：:The TRAF [tumor necrosis factor receptor-associated factor] family of cytoplasmic adaptor proteins link cell-surface receptors to intracellular signaling pathways that regulate innate and adaptive immune responses. In response to activation of RIG-I (retinoic acid-inducible gene I), a component of a pattern recognitio...

journal_title：Science signaling

authors： Zhang P,Reichardt A,Liang H,Aliyari R,Cheng D,Wang Y,Xu F,Cheng G,Liu Y

更新日期：2012-11-13 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：:Cerebral amyloid angiopathy (CAA) is a vascular dysfunction disorder characterized by deposits of amyloid-β (Aβ) in the walls of cerebral vessels. CAA and Aβ deposition in the brain parenchyma contribute to dementia and Alzheimer's disease (AD). We investigated the contribution of platelets, which accumulate at vascul...

journal_title：Science signaling

authors： Donner L,Fälker K,Gremer L,Klinker S,Pagani G,Ljungberg LU,Lothmann K,Rizzi F,Schaller M,Gohlke H,Willbold D,Grenegard M,Elvers M

更新日期：2016-05-24 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：: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：: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：:Skeletal muscle mass is regulated by activity, metabolism, and the availability of nutrients. During muscle atrophy, MNK2 expression increases. We found that MNK2 (mitogen-activated protein kinase-interacting kinase 2), but not MNK1, inhibited proteins involved in promoting protein synthesis, including eukaryotic tran...

journal_title：Science signaling

authors： Hu SI,Katz M,Chin S,Qi X,Cruz J,Ibebunjo C,Zhao S,Chen A,Glass DJ

更新日期：2012-02-14 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：: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 PAR-1-MARK pathway controls cell polarity through the phosphorylation of microtubule-associated proteins. Rho-Rac guanine nucleotide exchange factor 2 (ARHGEF2), which activates Ras homolog family member A (RHOA), is anchored to the microtubule network and sequestered in an inhibited state through binding to dynei...

journal_title：Science signaling

authors： Sandí MJ,Marshall CB,Balan M,Coyaud É,Zhou M,Monson DM,Ishiyama N,Chandrakumar AA,La Rose J,Couzens AL,Gingras AC,Raught B,Xu W,Ikura M,Morrison DK,Rottapel R

更新日期：2017-10-31 00:00:00

abstract：:Understanding the complex dynamics of growth factor signaling requires both mechanistic and kinetic information. Although signaling dynamics have been studied for pathways downstream of receptor tyrosine kinases and G protein (heterotrimeric guanine nucleotide-binding protein)-coupled receptors, they have not been inv...

journal_title：Science signaling

authors： Vizán P,Miller DS,Gori I,Das D,Schmierer B,Hill CS

更新日期：2013-12-10 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：: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：: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：: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：: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：:Transitional B cells must actively undergo selection for self-tolerance before maturing into their resting follicular B cell successors. We found that metabolic quiescence was acquired at the follicular B cell stage in both humans and mice. In follicular B cells, the expression of genes involved in ribosome biogenesis...

journal_title：Science signaling

authors： Farmer JR,Allard-Chamard H,Sun N,Ahmad M,Bertocchi A,Mahajan VS,Aicher T,Arnold J,Benson MD,Morningstar J,Barmettler S,Yuen G,Murphy SJH,Walter JE,Ghebremichael M,Shalek AK,Batista F,Gerszten R,Pillai S

更新日期：2019-10-22 00:00:00

abstract：:Group 3 innate lymphoid cells (ILC3s) are composed of subsets that are either positive or negative for the natural cytotoxicity receptor (NCR) NKp46 (encoded by Ncr1). ILC3s are located at mucosal sites, such as in the intestine and lung, where they are exposed to billions of commensal microbes and potentially harmful...

journal_title：Science signaling

authors： Viant C,Rankin LC,Girard-Madoux MJ,Seillet C,Shi W,Smyth MJ,Bartholin L,Walzer T,Huntington ND,Vivier E,Belz GT

更新日期：2016-05-03 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：:Fragile X syndrome (FXS) mental retardation is caused by loss-of-function mutations in an RNA-binding protein, fragile X mental retardation protein (FMRP). Previous studies in patients or animal models of FXS have identified alterations in dendritic spine structure, as well as synaptic plasticity induced by metabotrop...

journal_title：Science signaling

authors： Ronesi JA,Huber KM

更新日期：2008-02-05 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：:The interplay between calcium ion (Ca(2+)) and cyclic adenosine monophosphate (cAMP) signaling underlies crucial aspects of cell homeostasis. The membrane-bound Ca(2+)-regulated adenylyl cyclases (ACs) are pivotal points of this integration. These enzymes display high selectivity for Ca(2+) entry arising from the acti...

journal_title：Science signaling

authors： Willoughby D,Everett KL,Halls ML,Pacheco J,Skroblin P,Vaca L,Klussmann E,Cooper DM

更新日期：2012-04-10 00:00:00

abstract：:Adenosine 5'-diphosphate (ADP)-ribosylation is a protein posttranslational modification that is catalyzed by ADP-ribosyltransferases (ARTs), using nicotinamide adenine dinucleotide (NAD(+)) as a substrate. Mono-ribosylation can be extended into polymers of ADP-ribose (PAR). Poly(ADP-ribosyl)polymerase (PARP) 1, the be...

journal_title：Science signaling

authors： Hottiger MO,Boothby M,Koch-Nolte F,Lüscher B,Martin NM,Plummer R,Wang ZQ,Ziegler M

更新日期：2011-05-24 00:00:00

abstract：:TRPML1 (transient receptor potential mucolipin 1) is a Ca2+-permeable, nonselective cation channel localized to the membranes of endosomes and lysosomes and is not present or functional on the plasma membrane. Ca2+ released from endosomes and lysosomes into the cytosol through TRPML1 channels is vital for trafficking,...

journal_title：Science signaling

authors： Thakore P,Pritchard HAT,Griffin CS,Yamasaki E,Drumm BT,Lane C,Sanders KM,Feng Earley Y,Earley S

更新日期：2020-06-23 00:00:00

abstract：:Toll-like receptor (TLR) signaling regulates macrophage activation and effector cytokine propagation in the constrained environment of a tissue. In macrophage populations, TLR4 stimulates the dose-dependent transcription of nuclear factor κB (NF-κB) target genes. However, using single-RNA counting, we found that indiv...

journal_title：Science signaling

authors： Bagnall J,Boddington C,England H,Brignall R,Downton P,Alsoufi Z,Boyd J,Rowe W,Bennett A,Walker C,Adamson A,Patel NMX,O'Cualain R,Schmidt L,Spiller DG,Jackson DA,Müller W,Muldoon M,White MRH,Paszek P

更新日期：2018-07-24 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：: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：:MKK4 (mitogen-activated protein kinase kinase 4) is a pivotal upstream activator of c-Jun N-terminal kinase and p38. Here, we report that the abundance of MKK4 increases in senescent human diploid fibroblasts through enhanced translation. We identified four microRNAs (miR-15b, miR-24, miR-25, and miR-141) that target ...

journal_title：Science signaling

authors： Marasa BS,Srikantan S,Masuda K,Abdelmohsen K,Kuwano Y,Yang X,Martindale JL,Rinker-Schaeffer CW,Gorospe M

更新日期：2009-10-27 00:00:00