Controlling long-term signaling: receptor dynamics determine attenuation and refractory behavior of the TGF-β pathway.

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：: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

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

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：:Progression through mitosis depends on a large number of protein complexes that regulate the major structural and physiological changes necessary for faithful chromosome segregation. Most, if not all, of the mitotic processes are regulated by a set of mitotic protein kinases that control protein activity by phosphoryl...

journal_title：Science signaling

authors： Hegemann B,Hutchins JR,Hudecz O,Novatchkova M,Rameseder J,Sykora MM,Liu S,Mazanek M,Lénárt P,Hériché JK,Poser I,Kraut N,Hyman AA,Yaffe MB,Mechtler K,Peters JM

更新日期：2011-11-08 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：:Uncontrolled expression of type I interferon (IFN-I) drives autoimmunity, necessitating the need for tight regulation. In this issue, Cao et al reveal a role for the kinase HIPK2 in the transcriptional control of IFN-I during antiviral immune responses. ...

journal_title：Science signaling

authors： Best SM,Ponia SS

更新日期：2019-03-19 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：: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：: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：: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：: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：: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

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

更新日期：2011-03-29 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：:Precise regulation of nuclear factor κB (NF-κB) signaling is crucial for normal immune responses, and defective NF-κB activity underlies a range of immunodeficiencies. NF-κB is activated through two signaling cascades: the classical and noncanonical pathways. The classical pathway requires inhibitor of κB kinase β (IK...

journal_title：Science signaling

authors： Gray CM,Remouchamps C,McCorkell KA,Solt LA,Dejardin E,Orange JS,May MJ

更新日期：2014-02-04 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：: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：:ONC201 (also called TIC10) is a small molecule that inactivates the cell proliferation- and cell survival-promoting kinases Akt and ERK and induces cell death through the proapoptotic protein TRAIL. ONC201 is currently in early-phase clinical testing for various malignancies. We found through gene expression and prote...

journal_title：Science signaling

authors： Kline CL,Van den Heuvel AP,Allen JE,Prabhu VV,Dicker DT,El-Deiry WS

更新日期：2016-02-16 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：:The CLAVATA (CLV) and flagellin (flg) signaling pathways act through peptide ligands and closely related plasma membrane-localized receptor-like kinases (RLKs). The plant peptide CLV3 regulates stem cell homeostasis, whereas the bacterial flg22 peptide elicits defense responses. We applied multiparameter fluorescence ...

journal_title：Science signaling

authors： Somssich M,Ma Q,Weidtkamp-Peters S,Stahl Y,Felekyan S,Bleckmann A,Seidel CA,Simon R

更新日期：2015-08-04 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：: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：: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：:For the first 30 years since its discovery, reversible protein acetylation has been studied and understood almost exclusively in the context of histone modification and gene transcription. With the discovery of non-histone acetylated proteins and acetylation-modifying enzymes in cellular compartments outside the nucle...

journal_title：Science signaling

authors： Norris KL,Lee JY,Yao TP

更新日期：2009-11-17 00:00:00

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：: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

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

abstract：:Defects in the biogenesis of or transport through primary cilia affect Hedgehog protein signaling, and many Hedgehog pathway components traffic through or accumulate in cilia. The Hedgehog receptor Patched negatively regulates the activity and ciliary accumulation of Smoothened, a seven-transmembrane protein that is e...

journal_title：Science signaling

authors： Kim J,Hsia EY,Brigui A,Plessis A,Beachy PA,Zheng X

更新日期：2015-06-02 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：:Genetic diversity in human natural killer (NK) cell receptors is linked to resistance and susceptibility to many diseases. Here, we tested the effect of this diversity on the nanoscale organization of killer cell immunoglobulin-like receptors (KIRs). Using superresolution microscopy, we found that inhibitory KIRs enco...

journal_title：Science signaling

authors： Kennedy PR,Barthen C,Williamson DJ,Pitkeathly WTE,Hazime KS,Cumming J,Stacey KB,Hilton HG,Carrington M,Parham P,Davis DM

更新日期：2019-12-17 00:00:00

abstract：:Genetically encoded fluorescent sensors enable cell-specific measurements of ions and small molecules in real time. Cyclic adenosine monophosphate (cAMP) is one of the most important signaling molecules in virtually all cell types and organisms. We describe cAMPr, a new single-wavelength cAMP sensor. We developed cAMP...

journal_title：Science signaling

authors： Hackley CR,Mazzoni EO,Blau J

更新日期：2018-03-06 00:00:00

abstract：:Antigen-mediated stimulation of the T cell receptor (TCR) triggers activation of nuclear factor κB (NF-κB), a key transcriptional regulator of T cell proliferation and effector cell differentiation. TCR signaling to NF-κB requires both the Carma1-Bcl10-Malt1 (CBM) complex and the inhibitor of κB (IκB) kinase (IKK) com...

journal_title：Science signaling

authors： Paul S,Traver MK,Kashyap AK,Washington MA,Latoche JR,Schaefer BC

更新日期：2014-05-13 00:00:00