Structural basis for activation and inhibition of class I phosphoinositide 3-kinases.

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：:Insight into the signaling pathways that regulate de novo lipogenesis may lead to new treatments for hepatic steatosis. ...

journal_title：Science signaling

authors： Wong W

更新日期：2017-02-21 00:00:00

abstract：:Precise control of the activity and abundance of ubiquitin-conjugating enzymes (E2s) ensures fidelity in ubiquitin chain synthesis. In this issue of Science Signaling, Liess et al. demonstrate that the human anaphase-promoting complex (APC/C)-associated E2 UBE2S adopts an autoinhibited dimeric state that increases the...

journal_title：Science signaling

authors： Bremm A

更新日期：2020-10-20 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：: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

authors： Ioannou MS,Marat AL

更新日期：2012-04-24 00:00:00

abstract：:Fgr is a member of the Src family of nonreceptor tyrosine kinases, which are overexpressed and constitutively active in many human cancers. Fgr expression is restricted to myeloid hematopoietic cells and is markedly increased in a subset of bone marrow samples from patients with acute myeloid leukemia (AML). Here, we ...

journal_title：Science signaling

authors： Shen K,Moroco JA,Patel RK,Shi H,Engen JR,Dorman HR,Smithgall TE

更新日期：2018-10-23 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：: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：:Epithelial cell polarity is linked to the control of tissue growth and tumorigenesis. The tumor suppressor and cell polarity protein lethal-2-giant larvae (Lgl) promotes Hippo signaling and inhibits Notch signaling to restrict tissue growth in Drosophila melanogaster Notch signaling is greater in lgl mutant tissue tha...

journal_title：Science signaling

authors： Portela M,Yang L,Paul S,Li X,Veraksa A,Parsons LM,Richardson HE

更新日期：2018-06-05 00:00:00

abstract：:The proteasome plays a pivotal role in the cellular response to oxidative stress. Here, we used biochemical and mass spectrometric methods to investigate structural changes in the 26S proteasomes from yeast and mammalian cells exposed to hydrogen peroxide (H₂O₂). Oxidative stress induced the dissociation of the 20S co...

journal_title：Science signaling

authors： Wang X,Yen J,Kaiser P,Huang L

更新日期：2010-12-07 00:00:00

abstract：:The cytokine interleukin-22 (IL-22), which is a member of the IL-10 family, is produced exclusively by immune cells and activates signal transducer and activator of transcription 3 (STAT3) in nonimmune cells, such as hepatocytes, keratinocytes, and colonic epithelial cells, to drive various processes central to tissue...

journal_title：Science signaling

authors： Lim C,Hong M,Savan R

更新日期：2016-09-27 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：:Secretory cells, such as pancreatic beta cells, face the challenge of increasing protein synthesis severalfold during acute or chronic stimulation. This poses a burden on the endoplasmic reticulum (ER), the organelle where proinsulin synthesis and folding takes place. Thus, beta cells use various adaptive mechanisms t...

journal_title：Science signaling

authors： Eizirik DL,Cnop M

更新日期：2010-02-23 00:00:00

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

authors： Gough NR

更新日期：2008-11-18 00:00:00

abstract：:Cytosolic pattern recognition receptors (PRRs) sense intracellular nucleic acids from pathogens such as bacteria and viruses, which leads to the induction of type I interferon (IFN) responses that are essential for an effective immune response. Further, these PRR pathways can be aberrantly activated by self DNA, which...

journal_title：Science signaling

authors： Bowie A

更新日期：2012-03-06 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 C-terminal guanine nucleotide exchange factor (GEF) module of Trio (TrioC) transfers signals from the Gαq/11 subfamily of heterotrimeric G proteins to the small guanosine triphosphatase (GTPase) RhoA, enabling Gαq/11-coupled G protein-coupled receptors (GPCRs) to control downstream events, such as cell motility an...

journal_title：Science signaling

authors： Bandekar SJ,Arang N,Tully ES,Tang BA,Barton BL,Li S,Gutkind JS,Tesmer JJG

更新日期：2019-02-19 00:00:00

abstract：:By regulating gene expression, microRNAs (miRNAs) play pivotal roles in physiological and pathological processes. However, the regulation of miRNAs is elusive. miR-192 is a key regulator of renal fibrosis and hypertrophy in diabetic nephropathy. Natarajan et al. showed that the miR-192 gene contains an upstream region...

journal_title：Science signaling

authors： Dong Z

更新日期：2013-06-04 00:00:00

abstract：:Secreted IgD concentration depends on the presence of microbiota. ...

journal_title：Science signaling

authors： Mushegian AA

更新日期：2017-02-21 00:00:00

abstract：:The cytokines of the transforming growth factor-β (TGF-β) family promote the growth and differentiation of multiple tissues, but the role of only the founding member, TGF-β, in regulating the immune responses has been extensively studied. TGF-β is critical to prevent the spontaneous activation of self-reactive T cells...

journal_title：Science signaling

authors： Browning LM,Pietrzak M,Kuczma M,Simms CP,Kurczewska A,Refugia JM,Lowery DJ,Rempala G,Gutkin D,Ignatowicz L,Muranski P,Kraj P

更新日期：2018-08-28 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：:Type 1 diabetes mellitus (T1DM) is associated with chronic systemic inflammation and enhanced susceptibility to systemic bacterial infection (sepsis). We hypothesized that low insulin concentrations in T1DM trigger the enzyme 5-lipoxygenase (5-LO) to produce the lipid mediator leukotriene B4 (LTB4), which triggers sys...

journal_title：Science signaling

authors： Filgueiras LR,Brandt SL,Wang S,Wang Z,Morris DL,Evans-Molina C,Mirmira RG,Jancar S,Serezani CH

更新日期：2015-01-27 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：: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：:Vitamin D receptor represses basal autophagy in breast tissue, which is derepressed by vitamin D, slowing cancer progression. ...

journal_title：Science signaling

authors： Mushegian AA

更新日期：2017-03-21 00:00:00

abstract：:This year's signaling breakthroughs highlight insights into the pathogenesis or treatment of cancer, malaria, and neurodegenerative disorders; reveal molecular insights into cell death; and identify signals that could be leveraged to prevent plant parasitism or engineer bacteria as microbial fuel cells. ...

journal_title：Science signaling

authors： Adler EM

更新日期：2016-01-05 00:00:00

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

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

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：:The postsynaptic site of neurons is composed of more than 1500 proteins arranged in protein-protein interaction complexes, the composition of which is modulated by protein phosphorylation through the actions of complex signaling networks. Components of these networks function as key regulators of synaptic plasticity, ...

journal_title：Science signaling

authors： Li J,Wilkinson B,Clementel VA,Hou J,O'Dell TJ,Coba MP

更新日期：2016-08-09 00:00:00

abstract：:In lymphocytes, the kinase Mst1 is required for the proper organization of integrins in the plasma membrane at the leading edge of migrating cells, which is critical for lymphocyte trafficking. We found a functional link between the small G protein Rab13 and Mst1 in lymphocyte adhesion and migration. In response to st...

journal_title：Science signaling

authors： Nishikimi A,Ishihara S,Ozawa M,Etoh K,Fukuda M,Kinashi T,Katagiri K

更新日期：2014-07-29 00:00:00