4E-BP2 hardwires lymphocytes for rapamycin sensitivity.

abstract：:During T cell activation by antigen-presenting cells (APCs), the diverse spatiotemporal organization of components of T cell signaling pathways modulates the efficiency of activation. Here, we found that loss of the tyrosine kinase interleukin-2 (IL-2)-inducible T cell kinase (Itk) in mice altered the spatiotemporal d...

journal_title：Science signaling

authors： Singleton KL,Gosh M,Dandekar RD,Au-Yeung BB,Ksionda O,Tybulewicz VL,Altman A,Fowell DJ,Wülfing C

更新日期：2011-10-04 00:00:00

abstract：:The protein kinase ATM is a master regulator of the DNA damage response but also responds directly to oxidative stress. Loss of ATM causes ataxia telangiectasia, a neurodegenerative disorder with pleiotropic symptoms that include cerebellar dysfunction, cancer, diabetes, and premature aging. We genetically separated t...

journal_title：Science signaling

authors： Lee JH,Mand MR,Kao CH,Zhou Y,Ryu SW,Richards AL,Coon JJ,Paull TT

更新日期：2018-01-09 00:00:00

abstract：:Phosphoinositide 3-kinases (PI3Ks) are implicated in a broad spectrum of cellular activities, such as growth, proliferation, differentiation, migration, and metabolism. Activation of class I PI3Ks by mutation or overexpression correlates with the development and maintenance of various human cancers. These PI3Ks are he...

journal_title：Science signaling

authors： Vadas O,Burke JE,Zhang X,Berndt A,Williams RL

更新日期：2011-10-18 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：: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

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

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

authors： Thathiah A,De Strooper B

更新日期：2009-10-20 00:00:00

abstract：:Slit proteins act as repulsive axon guidance cues by activating receptors of the Roundabout (Robo) family. During early neurogenesis in Drosophila melanogaster, Slit prevents the growth cones of longitudinal tract neurons from inappropriately crossing the midline, thus restricting these cells to trajectories parallel ...

journal_title：Science signaling

authors： Manavalan MA,Jayasinghe VR,Grewal R,Bhat KM

更新日期：2017-06-20 00:00:00

abstract：:Vascular endothelial growth factors (VEGFs) regulate blood and lymphatic vessel development through VEGF receptors (VEGFRs). The VEGFR immunoglobulin homology domain 2 (D2) is critical for ligand binding, and D3 provides additional interaction sites. VEGF-B and placenta growth factor (PlGF) bind to VEGFR-1 with high a...

journal_title：Science signaling

authors： Anisimov A,Leppänen VM,Tvorogov D,Zarkada G,Jeltsch M,Holopainen T,Kaijalainen S,Alitalo K

更新日期：2013-07-02 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：: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：:Neutrophil extracellular trap (NET) formation can generate short-term, functional anucleate cytoplasts and trigger loss of cell viability. We demonstrated that the necroptotic cell death effector mixed lineage kinase domain-like (MLKL) translocated from the cytoplasm to the plasma membrane and stimulated downstream NA...

journal_title：Science signaling

authors： D'Cruz AA,Speir M,Bliss-Moreau M,Dietrich S,Wang S,Chen AA,Gavillet M,Al-Obeidi A,Lawlor KE,Vince JE,Kelliher MA,Hakem R,Pasparakis M,Williams DA,Ericsson M,Croker BA

更新日期：2018-09-04 00:00:00

abstract：:This two-part lecture introduces students to the scientific computing language MATLAB. Prior computer programming experience is not required. The lectures present basic concepts of computer programming logic that tend to cause difficulties for beginners in addition to concepts that relate specifically to the MATLAB la...

journal_title：Science signaling

authors： Sobie EA

更新日期：2011-09-13 00:00:00

abstract：:Mechanical loading of the skeleton is essential for the development, growth, and maintenance of strong, weight-bearing bones. Bone strength is plastic and can be modulated in adults, as illustrated by the increased bone mass in the playing arms of athletes as compared with their nonplaying arms. Our studies have shown...

journal_title：Science signaling

authors： Turner CH,Warden SJ,Bellido T,Plotkin LI,Kumar N,Jasiuk I,Danzig J,Robling AG

更新日期：2009-04-28 00:00:00

abstract：:The symbiotic interaction between Rhizobium bacteria and legume plants leads to the induction of a new developmental program: the formation of nitrogen-fixing root nodules. Nodulation is triggered by specific bacterial signals, the Nod factors, and integrates plant developmental regulatory pathways to reactivate diffe...

journal_title：Science signaling

authors： Crespi M,Frugier F

更新日期：2008-12-09 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：:Biophysical methods and x-ray crystallography have revealed that class A G protein-coupled receptors (GPCRs) can form homodimers. We combined computational approaches with receptor cross-linking, energy transfer, and a newly developed functional export assay to characterize the residues involved in the dimerization in...

journal_title：Science signaling

authors： Jin J,Momboisse F,Boncompain G,Koensgen F,Zhou Z,Cordeiro N,Arenzana-Seisdedos F,Perez F,Lagane B,Kellenberger E,Brelot A

更新日期：2018-05-08 00:00:00

abstract：:The extracellular Ca(2+)-sensing receptor (CaSR) plays a nonredundant role in the functions of the parathyroid gland (PTG) and the kidney. Severe hyperparathyroidism, premature death, and incomplete gene excision in Casr(-/-) mice have precluded the assessment of CaSR function in other tissues. We generated mice with ...

journal_title：Science signaling

authors： Chang W,Tu C,Chen TH,Bikle D,Shoback D

更新日期：2008-09-02 00:00:00

abstract：:Mineralocorticoid receptor (MR) antagonists are effective at treating heart failure. In this issue of Science Signaling, Oakley et al. provide new insight into their cardioprotective actions and highlight the importance of the opposing relationship between the MR and the related glucocorticoid receptor (GR) in the res...

journal_title：Science signaling

authors： Chapman KE

更新日期：2019-04-16 00:00:00

abstract：:A challenge for biomedical research is the development of pharmaceuticals that appropriately target disease mechanisms. Natural products can be a rich source of bioactive chemicals for medicinal applications but can act through unknown mechanisms and can be difficult to produce or obtain. To address these challenges, ...

journal_title：Science signaling

authors： Potts MB,Kim HS,Fisher KW,Hu Y,Carrasco YP,Bulut GB,Ou YH,Herrera-Herrera ML,Cubillos F,Mendiratta S,Xiao G,Hofree M,Ideker T,Xie Y,Huang LJ,Lewis RE,MacMillan JB,White MA

更新日期：2013-10-15 00:00:00

abstract：:The role of the mitochondrial Ca2+ uniporter (MCU) in physiologic cell proliferation remains to be defined. Here, we demonstrated that the MCU was required to match mitochondrial function to metabolic demands during the cell cycle. During the G1-S transition (the cycle phase with the highest mitochondrial ATP output),...

journal_title：Science signaling

authors： Koval OM,Nguyen EK,Santhana V,Fidler TP,Sebag SC,Rasmussen TP,Mittauer DJ,Strack S,Goswami PC,Abel ED,Grumbach IM

更新日期：2019-04-30 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：: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：:The V600E mutation in the kinase BRAF is frequently detected in melanomas and results in constitutive activation of BRAF, which then promotes cell proliferation by the mitogen-activated protein kinase signaling pathway. Although the BRAFV600E kinase inhibitor vemurafenib has remarkable antitumor activity in patients w...

journal_title：Science signaling

authors： Beck D,Niessner H,Smalley KS,Flaherty K,Paraiso KH,Busch C,Sinnberg T,Vasseur S,Iovanna JL,Drießen S,Stork B,Wesselborg S,Schaller M,Biedermann T,Bauer J,Lasithiotakis K,Weide B,Eberle J,Schittek B,Schadendorf D,G

更新日期：2013-01-29 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：:The endoplasmic reticulum (ER) has emerged as a critical regulator of cell survival. IRE1 is a transmembrane protein with kinase and RNase activities that is localized to the ER and that promotes resistance to ER stress. We showed a mechanism by which IRE1 conferred protection against ER stress-mediated cell death. IR...

journal_title：Science signaling

authors： Kanekura K,Ma X,Murphy JT,Zhu LJ,Diwan A,Urano F

更新日期：2015-06-23 00:00:00

abstract：:The discovery of feedback loops between signaling and gene expression is ushering in new quantitative models of cellular regulation. In a recent issue of Science Signaling, Sung et al. showed how positive feedback downstream of nuclear factor κB (NF-κB) signaling enhances the capacity of macrophages to scale their ant...

journal_title：Science signaling

authors： Tkach KE,Oyler JE,Altan-Bonnet G

更新日期：2014-02-18 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：:MicroRNAs (miRNAs), key posttranscriptional regulators of many biological processes, have been implicated in many diseases, including cancer. In a recent paper, Avraham and colleagues take a systems biology approach to determine whether and how miRNAs are involved in the regulation of oncogenic signaling networks down...

journal_title：Science signaling

authors： Herschkowitz JI,Fu X

更新日期：2011-07-26 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：: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