4-1BB costimulation promotes CAR T cell survival through noncanonical NF-κB signaling.

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：:DNAX-activating protein of 12 kD (DAP12) is an immunoreceptor tyrosine-based activation motif (ITAM)-containing adaptor protein found in myeloid cells and natural killer cells, and it couples to various receptors that mediate either cellular activation or inhibition. DAP12 inhibits Toll-like receptor (TLR) signaling, ...

journal_title：Science signaling

authors： Peng Q,Long CL,Malhotra S,Humphrey MB

更新日期：2013-08-20 00:00:00

abstract：:For decades, the fission yeast Schizosaccharomyces pombe has been used as an excellent model with which to explore how cellular growth is coordinated with the division cycle, a yet-unanswered question in biology. New studies in this organism show that TOR (target of rapamycin) kinase and stress-responsive MAPK (mitoge...

journal_title：Science signaling

authors： Shiozaki K

更新日期：2009-11-10 00:00:00

abstract：:Cancer-associated pain is debilitating. Understanding the mechanisms that cause it can inform drug development that may improve quality of life in patients. Here, we found that the reduced abundance of potassium channels called TRESK in dorsal root ganglion (DRG) neurons sensitized nociceptive sensory neurons and canc...

journal_title：Science signaling

authors： Yang Y,Li S,Jin ZR,Jing HB,Zhao HY,Liu BH,Liang YJ,Liu LY,Cai J,Wan Y,Xing GG

更新日期：2018-10-16 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：: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

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

abstract：:Educated natural killer (NK) cells have inhibitory receptors specific for self major histocompatibility complex (MHC) class I molecules and kill cancer cells more efficiently than do NK cells that do not have such receptors (hyporesponsive NK cells). The mechanism behind this functional empowerment through education h...

journal_title：Science signaling

authors： Staaf E,Hedde PN,Bagawath Singh S,Piguet J,Gratton E,Johansson S

更新日期：2018-02-13 00:00:00

abstract：:The cytoplasmic phosphatase PTPN22 (protein tyrosine phosphatase nonreceptor type 22) plays a key role in regulating lymphocyte homeostasis, which ensures that the total number of lymphocytes in the periphery remains relatively constant. Mutations in PTPN22 confer an increased risk of developing autoimmune diseases; h...

journal_title：Science signaling

authors： Brownlie RJ,Miosge LA,Vassilakos D,Svensson LM,Cope A,Zamoyska R

更新日期：2012-11-27 00:00:00

abstract：:MKK4 (mitogen-activated protein kinase kinase 4) is a pivotal upstream activator of c-Jun N-terminal kinase and p38. Here, we report that the abundance of MKK4 increases in senescent human diploid fibroblasts through enhanced translation. We identified four microRNAs (miR-15b, miR-24, miR-25, and miR-141) that target ...

journal_title：Science signaling

authors： Marasa BS,Srikantan S,Masuda K,Abdelmohsen K,Kuwano Y,Yang X,Martindale JL,Rinker-Schaeffer CW,Gorospe M

更新日期：2009-10-27 00:00:00

abstract：:Alzheimer's disease (AD) is a progressive dementia disorder characterized by synaptic degeneration and amyloid-β (Aβ) accumulation in the brain. Through whole-genome sequencing of 1345 individuals from 410 families with late-onset AD (LOAD), we identified three highly penetrant variants in PRKCA, the gene that encodes...

journal_title：Science signaling

authors： Alfonso SI,Callender JA,Hooli B,Antal CE,Mullin K,Sherman MA,Lesné SE,Leitges M,Newton AC,Tanzi RE,Malinow R

更新日期：2016-05-10 00:00:00

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

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

abstract：:Myeloproliferative neoplasms (MPNs) frequently have an activating mutation in the gene encoding Janus kinase 2 (JAK2). Thus, targeting the pathway mediated by JAK and its downstream substrate, signal transducer and activator of transcription (STAT), may yield clinical benefit for patients with MPNs containing the JAK2...

journal_title：Science signaling

authors： Winter PS,Sarosiek KA,Lin KH,Meggendorfer M,Schnittger S,Letai A,Wood KC

更新日期：2014-12-23 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：:Endothelial cell dysfunction, characterized by a diminished response to endothelial cell-dependent vasodilators, is a hallmark of hypertension. TRPV4 channels play a major role in endothelial-dependent vasodilation, a function mediated by local Ca(2+) influx through clusters of functionally coupled TRPV4 channels rath...

journal_title：Science signaling

authors： Sonkusare SK,Dalsgaard T,Bonev AD,Hill-Eubanks DC,Kotlikoff MI,Scott JD,Santana LF,Nelson MT

更新日期：2014-07-08 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：:Under drought stress, abscisic acid (ABA) triggers closure of leaf cell pores called stomata, which are formed by two specialized cells called guard cells in plant epidermis. Two pathways downstream of ABA stimulate phosphorylation of the S-type anion channels SLAC1 (slow anion channel associated 1) and SLAH3 (SLAC1 h...

journal_title：Science signaling

authors： Maierhofer T,Diekmann M,Offenborn JN,Lind C,Bauer H,Hashimoto K,S Al-Rasheid KA,Luan S,Kudla J,Geiger D,Hedrich R

更新日期：2014-09-09 00:00:00

abstract：:Epigenetic modifications, such as DNA cytosine methylation, contribute to the mechanisms underlying learning and memory by coordinating adaptive gene expression and neuronal plasticity. Transcription-dependent plasticity regulated by DNA methylation includes synaptic plasticity and homeostatic synaptic scaling. Memory...

journal_title：Science signaling

authors： Meadows JP,Guzman-Karlsson MC,Phillips S,Brown JA,Strange SK,Sweatt JD,Hablitz JJ

更新日期：2016-08-23 00:00:00

abstract：:The scattering of cultured epithelial cells in response to hepatocyte growth factor (HGF) is a model system that recapitulates key features of metastatic cell behavior in vitro, including disruption of cell-cell adhesions and induction of cell migration. We have developed image analysis tools that do not require fluor...

journal_title：Science signaling

authors： Loerke D,le Duc Q,Blonk I,Kerstens A,Spanjaard E,Machacek M,Danuser G,de Rooij J

更新日期：2012-07-03 00:00:00

abstract：:The CXC chemokine CXCL12 mediates the chemoattraction of T cells and enhances the stimulation of T cells through the T cell receptor (TCR). The adaptor SLP-76 [Src homology 2 (SH2) domain-containing leukocyte protein of 76 kD] has two key tyrosine residues, Tyr(113) and Tyr(128), that mediate signaling downstream of t...

journal_title：Science signaling

authors： Smith X,Schneider H,Köhler K,Liu H,Lu Y,Rudd CE

更新日期：2013-07-30 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：:The mitogen-activated protein kinase (MAPK) extracellular signal-regulated kinase 2 (ERK2) is ubiquitously expressed in mammalian tissues and is involved in a wide range of biological processes. Although MAPKs have been intensely studied, identification of their substrates remains challenging. We have optimized a chem...

journal_title：Science signaling

authors： Carlson SM,Chouinard CR,Labadorf A,Lam CJ,Schmelzle K,Fraenkel E,White FM

更新日期：2011-10-25 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：:Transforming growth factor-β (TGF-β) is a pluripotent cytokine that regulates cell fate and plasticity in normal tissues and tumors. The multifunctional cellular responses evoked by TGF-β are mediated by the canonical SMAD pathway and by noncanonical pathways, including mitogen-activated protein kinase (MAPK) pathways...

journal_title：Science signaling

authors： Hamidi A,Song J,Thakur N,Itoh S,Marcusson A,Bergh A,Heldin CH,Landström M

更新日期：2017-07-04 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：:Regulatory T (T(reg)) cells are a unique CD4(+) T cell lineage that plays a crucial role in the maintenance of immunological tolerance. The Forkhead box transcription factor Foxp3 is critically involved in T(reg) cell development and responsible for determining the suppressive function of these cells. The majority of ...

journal_title：Science signaling

authors： Toker A,Huehn J

更新日期：2011-02-01 00:00:00

abstract：:Intracellular calcium (Ca2+) signals are of prime importance for cellular function and behavior and are underpinned by a plethora of Ca2+ channels, pumps, transporters, and binding proteins that are regulated in complex ways. A series of biennial meetings, the International Meetings of the European Calcium Society (EC...

journal_title：Science signaling

authors： Parys JB,Guse AH

更新日期：2019-09-17 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：: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 diacylglycerol kinases (DGKs) attenuate diacylglycerol (DAG)-mediated signals by catalyzing the conversion of DAG to phosphatidic acid. In T lymphocytes, the antigen-stimulated generation of DAG links signal strength to the intensity and duration of signaling by the Ras-extracellular signal-regulated kinase (ERK) ...

journal_title：Science signaling

authors： Mérida I,Andrada E,Gharbi SI,Ávila-Flores A

更新日期：2015-04-28 00:00:00

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