Lack of the phosphatase PTPN22 increases adhesion of murine regulatory T cells to improve their immunosuppressive function.

abstract：:GIV (Gα-interacting vesicle-associated protein; also known as Girdin) enhances Akt activation downstream of multiple growth factor- and G protein (heterotrimeric guanosine 5'-triphosphate-binding protein)-coupled receptors to trigger cell migration and cancer invasion. We demonstrate that GIV is a tyrosine phosphoprot...

journal_title：Science signaling

authors： Lin C,Ear J,Pavlova Y,Mittal Y,Kufareva I,Ghassemian M,Abagyan R,Garcia-Marcos M,Ghosh P

更新日期：2011-09-27 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：: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：:The prevalence, presentation, and progression of Alzheimer's disease (AD) differ between men and women, although β-amyloid (Aβ) deposition is a pathological hallmark of AD in both sexes. Aβ-induced activation of the neuronal glutamate receptor mGluR5 is linked to AD progression. However, we found that mGluR5 exhibits ...

journal_title：Science signaling

authors： Abd-Elrahman KS,Albaker A,de Souza JM,Ribeiro FM,Schlossmacher MG,Tiberi M,Hamilton A,Ferguson SSG

更新日期：2020-12-15 00:00:00

abstract：:Spontaneous neural differentiation of embryonic stem cells is induced by Noggin-mediated inhibition of bone morphogenetic protein 4 (BMP4) signaling. RhoA is a guanosine triphosphatase (GTPase) that regulates cytoskeletal dynamics and gene expression, both of which control stem cell fate. We found that disruption of S...

journal_title：Science signaling

authors： Yang J,Wu C,Stefanescu I,Jakobsson L,Chervoneva I,Horowitz A

更新日期：2016-07-26 00:00:00

abstract：:Exosomes are paracrine regulators of the tumor microenvironment and contain complex cargo. We previously reported that exosomes released from acute myeloid leukemia (AML) cells can suppress residual hematopoietic stem and progenitor cell (HSPC) function indirectly through stromal reprogramming of niche retention facto...

journal_title：Science signaling

authors： Hornick NI,Doron B,Abdelhamed S,Huan J,Harrington CA,Shen R,Cambronne XA,Chakkaramakkil Verghese S,Kurre P

更新日期：2016-09-06 00:00:00

abstract：:Clinical response to chimeric antigen receptor (CAR) T cell therapy is correlated with CAR T cell persistence, especially for CAR T cells that target CD19+ hematologic malignancies. 4-1BB-costimulated CAR (BBζ) T cells exhibit longer persistence after adoptive transfer than do CD28-costimulated CAR (28ζ) T cells. 4-1B...

journal_title：Science signaling

authors： Philipson BI,O'Connor RS,May MJ,June CH,Albelda SM,Milone MC

更新日期：2020-03-31 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：: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：:A central component of receptor-evoked Ca(2+) signaling is store-operated Ca(2+) entry (SOCE), which is activated by the assembly of STIM1-Orai1 channels in endoplasmic reticulum (ER) and plasma membrane (PM) (ER-PM) junctions in response to depletion of ER Ca(2+). We report that STIM2 enhances agonist-mediated activa...

journal_title：Science signaling

authors： Ong HL,de Souza LB,Zheng C,Cheng KT,Liu X,Goldsmith CM,Feske S,Ambudkar IS

更新日期：2015-01-13 00:00:00

abstract：:The mTORC1 [mammalian (or mechanistic) target of rapamycin complex 1] inhibitor rapamycin is a potent inhibitor of T and B lymphocyte growth and proliferation. In this issue of Science Signaling, So et al found that the isoform of 4E-BP (4E-BP2) in lymphocytes that regulates messenger RNA translation is more sensitive...

journal_title：Science signaling

authors： Abraham RT

更新日期：2016-05-31 00:00:00

abstract：:Manipulating ligand interactions with the activating receptor NKG2D modulates natural killer cell responses. ...

journal_title：Science signaling

authors： Foley JF

更新日期：2017-05-30 00:00:00

abstract：:MicroRNAs (miRNAs) are small noncoding RNAs that suppress the abundance of partially complementary mRNAs and inhibit their translation. Each miRNA can regulate hundreds of mRNAs, sometimes strongly but often weakly, to mediate a diverse array of biological functions, including proliferation, cell signaling, differenti...

journal_title：Science signaling

authors： Hata A,Lieberman J

更新日期：2015-03-17 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：: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：:Acute cardiorespiratory responses to O2 deficiency are essential for physiological homeostasis. The prototypical acute O2-sensing organ is the carotid body, which contains glomus cells expressing K+ channels whose inhibition by hypoxia leads to transmitter release and activation of nerve fibers terminating in the brai...

journal_title：Science signaling

authors： Moreno-Domínguez A,Ortega-Sáenz P,Gao L,Colinas O,García-Flores P,Bonilla-Henao V,Aragonés J,Hüttemann M,Grossman LI,Weissmann N,Sommer N,López-Barneo J

更新日期：2020-01-21 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：: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：: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：:The guanosine triphosphatases of the Rho and Rac subfamilies regulate protumorigenic pathways and are activated by guanine nucleotide exchange factors (Rho GEFs), which could be potential targets for anticancer therapies. We report that two Rho GEFs, Vav2 and Vav3, play synergistic roles in breast cancer by sustaining...

journal_title：Science signaling

authors： Citterio C,Menacho-Márquez M,García-Escudero R,Larive RM,Barreiro O,Sánchez-Madrid F,Paramio JM,Bustelo XR

更新日期：2012-10-02 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：:The accumulation of damaged or excess proteins and organelles is a defining feature of metabolic disease in nearly every tissue. Thus, a central challenge in maintaining metabolic homeostasis is the identification, sequestration, and degradation of these cellular components, including protein aggregates, mitochondria,...

journal_title：Science signaling

authors： Evans TD,Sergin I,Zhang X,Razani B

更新日期：2017-02-28 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：:The detection of microbes and initiation of an innate immune response occur through pattern recognition receptors (PRRs), which are critical for the production of inflammatory cytokines and activation of the cellular microbicidal machinery. In particular, the production of reactive oxygen species (ROS) by the NADPH ox...

journal_title：Science signaling

authors： Billings EA,Lee CS,Owen KA,D'Souza RS,Ravichandran KS,Casanova JE

更新日期：2016-02-02 00:00:00

abstract：:Jiang et al. (Research Article, 11 October 2011, DOI: 10.1126/scisignal.2002152) used a combined experimental and computational modeling approach to study the dynamic response behavior of covalent modification cycles in the presence of downstream targets ("loads"). Despite remarkable agreement between experiments and ...

journal_title：Science signaling

authors： Straube R

更新日期：2012-01-03 00:00:00

abstract：:TRPM2 is a Ca2+-permeable cation channel that is specifically activated by adenosine diphosphoribose (ADPR). Channel activation in the plasma membrane leads to Ca2+ influx and has been linked to apoptotic mechanisms. The primary agonist, ADPR, is produced both extra- and intracellularly and causes increases in intrace...

journal_title：Science signaling

authors： Lange I,Yamamoto S,Partida-Sanchez S,Mori Y,Fleig A,Penner R

更新日期：2009-05-19 00:00:00

abstract：:Individual signaling pathways operate in the context of the broader signaling network. Thus, the response of a cell to signals from the environment is affected by the state of the signaling network, such as the clinically relevant example of whether some components in the network are inhibited. The cytokine tumor necr...

journal_title：Science signaling

authors： Gierut JJ,Wood LB,Lau KS,Lin YJ,Genetti C,Samatar AA,Lauffenburger DA,Haigis KM

更新日期：2015-12-15 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：: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：:Chemokines were initially thought of only as regulators of the migration of developing thymocytes between different compartments of the thymus and were predicted also to be involved in early stages of thymocyte development. Recent data have suggested additional functions for the chemokine receptor CXCR4-a G protein-co...

journal_title：Science signaling

authors： Ahamed JA,Madhivadhani P

更新日期：2010-04-27 00:00:00