Novel p47(phox)-related organizers regulate localized NADPH oxidase 1 (Nox1) activity.

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) and Tks5 are functional members of a p47(phox)-related organizer superfamily. Tks proteins selectively support Nox1 and Nox3 (and not Nox2 and Nox4) activity in reconstituted cellular systems and interact with the NoxA1 activator protein through an Src homology 3 domain-mediated interaction. Endogenous Tks4 is required for Rac guanosine triphosphatase- and Nox1-dependent ROS production by DLD1 colon cancer cells. Our results are consistent with the Tks-mediated recruitment of Nox1 to invadopodia that form in DLD1 cells in a Tks- and Nox-dependent fashion. We propose that Tks organizers represent previously unrecognized members of an organizer superfamily that link Nox to localized ROS formation.

journal_name

Sci Signal

journal_title

Science signaling

authors

Gianni D,Diaz B,Taulet N,Fowler B,Courtneidge SA,Bokoch GM

doi

10.1126/scisignal.2000370

subject

Has Abstract

pub_date

2009-09-15 00:00:00

pages

ra54

issue

88

eissn

1945-0877

issn

1937-9145

pii

2/88/ra54

journal_volume

2

pub_type

杂志文章
  • Manganese promotes the aggregation and prion-like cell-to-cell exosomal transmission of α-synuclein.

    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

    pub_type: 杂志文章

    doi:10.1126/scisignal.aau4543

    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

  • Transforming growth factor-β and Notch ligands act as opposing environmental cues in regulating the plasticity of type 3 innate lymphoid cells.

    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

    pub_type: 杂志文章

    doi:10.1126/scisignal.aaf2176

    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

  • c-MYC suppresses BIN1 to release poly(ADP-ribose) polymerase 1: a mechanism by which cancer cells acquire cisplatin resistance.

    abstract::Cancer cells acquire resistance to DNA-damaging therapeutic agents, such as cisplatin, but the genetic mechanisms through which this occurs remain unclear. We show that the c-MYC oncoprotein increases cisplatin resistance by decreasing production of the c-MYC inhibitor BIN1 (bridging integrator 1). The sensitivity of ...

    journal_title:Science signaling

    pub_type: 杂志文章

    doi:10.1126/scisignal.2001556

    authors: Pyndiah S,Tanida S,Ahmed KM,Cassimere EK,Choe C,Sakamuro D

    更新日期:2011-03-29 00:00:00

  • Focus issue: fine-tuning Hedgehog signaling in development and disease.

    abstract::Hedgehog (Hh) signaling plays varied and critical roles in animal development, homeostasis, and disease. The core components of the canonical pathway and many key modulators of signaling have been identified, as have mechanisms by which the quantity and quality of signaling through the pathway are modulated. New resea...

    journal_title:Science signaling

    pub_type: 社论

    doi:10.1126/scisignal.2002653

    authors: VanHook AM

    更新日期:2011-11-22 00:00:00

  • Phosphorylation of Mad controls competition between wingless and BMP signaling.

    abstract::Bone morphogenetic proteins (BMPs) and Wnts are growth factors that provide essential patterning signals for cell proliferation and differentiation. Here, we describe a molecular mechanism by which the phosphorylation state of the Drosophila transcription factor Mad determines its ability to transduce either BMP or Wi...

    journal_title:Science signaling

    pub_type: 杂志文章

    doi:10.1126/scisignal.2002034

    authors: Eivers E,Demagny H,Choi RH,De Robertis EM

    更新日期:2011-10-11 00:00:00

  • The second messenger c-di-AMP inhibits the osmolyte uptake system OpuC in Staphylococcus aureus.

    abstract::Staphylococcus aureus is an important opportunistic human pathogen that is highly resistant to osmotic stresses. To survive an increase in osmolarity, bacteria immediately take up potassium ions and small organic compounds known as compatible solutes. The second messenger cyclic diadenosine monophosphate (c-di-AMP) re...

    journal_title:Science signaling

    pub_type: 杂志文章

    doi:10.1126/scisignal.aaf7279

    authors: Schuster CF,Bellows LE,Tosi T,Campeotto I,Corrigan RM,Freemont P,Gründling A

    更新日期:2016-08-16 00:00:00

  • The adaptor protein insulin receptor substrate 2 inhibits alternative macrophage activation and allergic lung inflammation.

    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

    pub_type: 杂志文章

    doi:10.1126/scisignal.aad6724

    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

  • Mechanochemotransduction during cardiomyocyte contraction is mediated by localized nitric oxide signaling.

    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

    pub_type: 杂志文章

    doi:10.1126/scisignal.2005046

    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

  • Degrons in cancer.

    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

    pub_type: 杂志文章,评审

    doi:10.1126/scisignal.aak9982

    authors: Mészáros B,Kumar M,Gibson TJ,Uyar B,Dosztányi Z

    更新日期:2017-03-14 00:00:00

  • Integrative analysis of kinase networks in TRAIL-induced apoptosis provides a source of potential targets for combination therapy.

    abstract::Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is an endogenous secreted peptide and, in preclinical studies, preferentially induces apoptosis in tumor cells rather than in normal cells. The acquisition of resistance in cells exposed to TRAIL or its mimics limits their clinical efficacy. Because kinas...

    journal_title:Science signaling

    pub_type: 杂志文章

    doi:10.1126/scisignal.2005700

    authors: So J,Pasculescu A,Dai AY,Williton K,James A,Nguyen V,Creixell P,Schoof EM,Sinclair J,Barrios-Rodiles M,Gu J,Krizus A,Williams R,Olhovsky M,Dennis JW,Wrana JL,Linding R,Jorgensen C,Pawson T,Colwill K

    更新日期:2015-04-07 00:00:00

  • Hypusine biosynthesis in β cells links polyamine metabolism to facultative cellular proliferation to maintain glucose homeostasis.

    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

    pub_type: 杂志文章

    doi:10.1126/scisignal.aax0715

    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

  • The role of EHD proteins at the neuronal synapse.

    abstract::Eps15 homology domain (EHD) proteins are conserved adenosine triphosphatases that are involved in membrane remodeling. EHD family members are structurally similar to the guanosine triphosphatase (GTPase) dynamin, and both are essential for the fission step of clathrin-mediated endocytosis. This Journal Club highlights...

    journal_title:Science signaling

    pub_type: 杂志文章,评审

    doi:10.1126/scisignal.2002989

    authors: Ioannou MS,Marat AL

    更新日期:2012-04-24 00:00:00

  • Focus issue: an expanding world for TGF-beta signaling.

    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

    pub_type: 社论

    doi:10.1126/scisignal.146eg8

    authors: Gough NR

    更新日期:2008-11-18 00:00:00

  • Temperature-activated ion channels in neural crest cells confer maternal fever-associated birth defects.

    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

    pub_type: 杂志文章

    doi:10.1126/scisignal.aal4055

    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

  • Ubiquitin-dependent endocytosis of NKG2D-DAP10 receptor complexes activates signaling and functions in human NK cells.

    abstract::Cytotoxic lymphocytes share the presence of the activating receptor NK receptor group 2, member D (NKG2D) and the signaling-competent adaptor DNAX-activating protein 10 (DAP10), which together play an important role in antitumor immune surveillance. Ligand stimulation induces the internalization of NKG2D-DAP10 complex...

    journal_title:Science signaling

    pub_type: 杂志文章

    doi:10.1126/scisignal.aab2724

    authors: Quatrini L,Molfetta R,Zitti B,Peruzzi G,Fionda C,Capuano C,Galandrini R,Cippitelli M,Santoni A,Paolini R

    更新日期:2015-10-27 00:00:00

  • G protein-coupled receptors, cholinergic dysfunction, and Abeta toxicity in Alzheimer's disease.

    abstract::The beta-amyloid (Abeta) peptide is associated with the pathogenesis of Alzheimer's disease (AD). Evidence gathered over the last two decades suggests that the gradual accumulation of soluble and insoluble Abeta peptide species triggers a cascade of events that leads to the clinical manifestation of AD. Abeta accumula...

    journal_title:Science signaling

    pub_type: 杂志文章,评审

    doi:10.1126/scisignal.293re8

    authors: Thathiah A,De Strooper B

    更新日期:2009-10-20 00:00:00

  • Casein kinase 2 (CK2) phosphorylates the deubiquitylase OTUB1 at Ser16 to trigger its nuclear localization.

    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

    pub_type: 杂志文章

    doi:10.1126/scisignal.aaa0441

    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

  • Pressure-induced oxidative activation of PKG enables vasoregulation by Ca2+ sparks and BK channels.

    abstract::Activation of Ca2+-sensitive, large-conductance potassium (BK) channels in vascular smooth muscle cells (VSMCs) by local, ryanodine receptor-mediated Ca2+ signals (Ca2+ sparks) acts as a brake on pressure-induced (myogenic) vasoconstriction-a fundamental mechanism that regulates blood flow in small resistance arteries...

    journal_title:Science signaling

    pub_type: 杂志文章

    doi:10.1126/scisignal.aaf6625

    authors: Khavandi K,Baylie RA,Sugden SA,Ahmed M,Csato V,Eaton P,Hill-Eubanks DC,Bonev AD,Nelson MT,Greenstein AS

    更新日期:2016-10-11 00:00:00

  • Extensive crosstalk between O-GlcNAcylation and phosphorylation regulates cytokinesis.

    abstract::Like phosphorylation, the addition of O-linked beta-N-acetylglucosamine (O-GlcNAcylation) is a ubiquitous, reversible process that modifies serine and threonine residues on nuclear and cytoplasmic proteins. Overexpression of the enzyme that adds O-GlcNAc to target proteins, O-GlcNAc transferase (OGT), perturbs cytokin...

    journal_title:Science signaling

    pub_type: 杂志文章

    doi:10.1126/scisignal.2000526

    authors: Wang Z,Udeshi ND,Slawson C,Compton PD,Sakabe K,Cheung WD,Shabanowitz J,Hunt DF,Hart GW

    更新日期:2010-01-12 00:00:00

  • Tumors block pain with CXCL12.

    abstract::The chemokine CXCL12 released from early stage pancreatic cancer recruits Schwann cells and suppresses pain signaling. ...

    journal_title:Science signaling

    pub_type: 评论,杂志文章

    doi:10.1126/scisignal.aam7233

    authors: Gough NR

    更新日期:2017-01-10 00:00:00

  • Dysregulation of microRNA biogenesis and gene silencing in cancer.

    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

    pub_type: 杂志文章,评审

    doi:10.1126/scisignal.2005825

    authors: Hata A,Lieberman J

    更新日期:2015-03-17 00:00:00

  • 4E-BP2 hardwires lymphocytes for rapamycin sensitivity.

    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

    pub_type: 评论,杂志文章,评审

    doi:10.1126/scisignal.aaf8190

    authors: Abraham RT

    更新日期:2016-05-31 00:00:00

  • Rounding up the usual suspects in O2 sensing: CO, NO, and H2S!

    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

    pub_type: 评论,杂志文章

    doi:10.1126/scisignal.aab1665

    authors: Fandrey J

    更新日期:2015-04-21 00:00:00

  • Aβ oligomers induce pathophysiological mGluR5 signaling in Alzheimer's disease model mice in a sex-selective manner.

    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

    pub_type: 杂志文章

    doi:10.1126/scisignal.abd2494

    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

  • Inhibition of the oncogenic fusion protein EWS-FLI1 causes G2-M cell cycle arrest and enhanced vincristine sensitivity in Ewing's sarcoma.

    abstract::Ewing's sarcoma (ES) is a rare and highly malignant cancer that grows in the bones or surrounding tissues mostly affecting adolescents and young adults. A chimeric fusion between the RNA binding protein EWS and the ETS family transcription factor FLI1 (EWS-FLI1), which is generated from a chromosomal translocation, is...

    journal_title:Science signaling

    pub_type: 杂志文章

    doi:10.1126/scisignal.aam8429

    authors: Zöllner SK,Selvanathan SP,Graham GT,Commins RMT,Hong SH,Moseley E,Parks S,Haladyna JN,Erkizan HV,Dirksen U,Hogarty MD,Üren A,Toretsky JA

    更新日期:2017-10-03 00:00:00

  • Measurement of phosphorylated extracellular signal-regulated kinase 1 and 2 in an undergraduate teaching laboratory with ALPHAscreen technology.

    abstract::Teaching the practical aspects of signal transduction to large undergraduate classes can be challenging when there is only a finite time frame in which to engage in laboratory activities. This teaching resource describes the use of bead-based ALPHAscreen technology for a class of 300 second-year biochemistry students,...

    journal_title:Science signaling

    pub_type: 杂志文章

    doi:10.1126/scisignal.262tr1

    authors: Hay DL

    更新日期:2009-03-17 00:00:00

  • Human regulatory T cells rapidly suppress T cell receptor-induced Ca(2+), NF-κB, and NFAT signaling in conventional T cells.

    abstract::CD4(+)CD25(hi)Foxp3(+) regulatory T cells (T(regs)) are critical mediators of self-tolerance, which is crucial for the prevention of autoimmune disease, but T(regs) can also inhibit antitumor immunity. T(regs) inhibit the proliferation of CD4(+)CD25(-) conventional T cells (T(cons)), as well as the ability of these ce...

    journal_title:Science signaling

    pub_type: 杂志文章

    doi:10.1126/scisignal.2002179

    authors: Schmidt A,Oberle N,Weiss EM,Vobis D,Frischbutter S,Baumgrass R,Falk CS,Haag M,Brügger B,Lin H,Mayr GW,Reichardt P,Gunzer M,Suri-Payer E,Krammer PH

    更新日期:2011-12-20 00:00:00

  • Quantitative analysis of competitive cytokine signaling predicts tissue thresholds for the propagation of macrophage activation.

    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

    pub_type: 杂志文章

    doi:10.1126/scisignal.aaf3998

    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

  • Quantitative kinase and phosphatase profiling reveal that CDK1 phosphorylates PP2Ac to promote mitotic entry.

    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

    pub_type: 杂志文章

    doi:10.1126/scisignal.aba7823

    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

  • LRP6 mediates cAMP generation by G protein-coupled receptors through regulating the membrane targeting of Gα(s).

    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

    pub_type: 杂志文章

    doi:10.1126/scisignal.2001464

    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