Phosphoproteomic analysis of chimeric antigen receptor signaling reveals kinetic and quantitative differences that affect cell function.

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

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

abstract：:Chemokines were initially thought of only as regulators of the migration of developing thymocytes between different compartments of the thymus and were predicted also to be involved in early stages of thymocyte development. Recent data have suggested additional functions for the chemokine receptor CXCR4-a G protein-co...

journal_title：Science signaling

authors： Ahamed JA,Madhivadhani P

更新日期：2010-04-27 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：: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：:Dimers of conventional transforming growth factor-β (TGF-β) and bone morphogenetic protein (BMP) ligands are composed of two 100- to 140-amino acid peptides that are produced through the proteolytic processing of a proprotein precursor by proconvertases, such as furin. We report the identification of an evolutionarily...

journal_title：Science signaling

authors： Akiyama T,Marqués G,Wharton KA

更新日期：2012-04-03 00:00:00

abstract：:Compared with the luminal subtype, the basal-like subtype of breast cancer has an aggressive clinical behavior, but the reasons for this difference between the two subtypes are poorly understood. We identified microRNAs (miRNAs) miR-221 and miR-222 (miR-221/222) as basal-like subtype-specific miRNAs that decrease expr...

journal_title：Science signaling

authors： Stinson S,Lackner MR,Adai AT,Yu N,Kim HJ,O'Brien C,Spoerke J,Jhunjhunwala S,Boyd Z,Januario T,Newman RJ,Yue P,Bourgon R,Modrusan Z,Stern HM,Warming S,de Sauvage FJ,Amler L,Yeh RF,Dornan D

更新日期：2011-08-09 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：:Skeletal muscle mass is regulated by activity, metabolism, and the availability of nutrients. During muscle atrophy, MNK2 expression increases. We found that MNK2 (mitogen-activated protein kinase-interacting kinase 2), but not MNK1, inhibited proteins involved in promoting protein synthesis, including eukaryotic tran...

journal_title：Science signaling

authors： Hu SI,Katz M,Chin S,Qi X,Cruz J,Ibebunjo C,Zhao S,Chen A,Glass DJ

更新日期：2012-02-14 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：: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：: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

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

abstract：:The role of mucin 1 (MUC1) in protecting epithelia from microbial infection, enzymatic digestion, and other irritants has been appreciated for some time. In addition, MUC1 serves as a barrier to embryo implantation. MUC1 is highly abundant in many tumors in which its role in barrier function may serve to protect cells...

journal_title：Science signaling

authors： Carson DD

更新日期：2008-07-08 00:00:00

abstract：:Stress is an important contributor to pathological conditions in humans. Hormonal changes that occur during acute and chronic stress situations can affect glucose homeostasis in both healthy people and in those with diabetes. Several studies have reported a negative effect of acute stress on maintenance of blood gluco...

journal_title：Science signaling

authors： Marcovecchio ML,Chiarelli F

更新日期：2012-10-23 00:00:00

abstract：:The vascular endothelial growth factor (VEGF) signaling pathway plays a pivotal role in normal development and also represents a major therapeutic target for tumors and intraocular neovascular disorders. The VEGF receptor tyrosine kinases promote angiogenesis by phosphorylating downstream proteins in endothelial cells...

journal_title：Science signaling

authors： Zhuang G,Yu K,Jiang Z,Chung A,Yao J,Ha C,Toy K,Soriano R,Haley B,Blackwood E,Sampath D,Bais C,Lill JR,Ferrara N

更新日期：2013-04-16 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 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：: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 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：:Pentraxin 3 (PTX3), a member of the long pentraxin subfamily within the family of pentraxins, is a soluble pattern recognition molecule that functions in the innate immune system. Innate immunity affords the infected host protection against sepsis, a potentially life-threatening inflammatory response to infection. Ext...

journal_title：Science signaling

authors： Daigo K,Nakakido M,Ohashi R,Fukuda R,Matsubara K,Minami T,Yamaguchi N,Inoue K,Jiang S,Naito M,Tsumoto K,Hamakubo T

更新日期：2014-09-16 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：: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：: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：: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

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

abstract：:In a mouse model of Parkinson's disease, new evidence shows that l-DOPA, which is used to treat the symptoms of the disease but also causes dyskinesia, results in a persistent activation of the protein kinase mTOR (mammalian target of rapamycin) in a subset of striatal medium spiny neurons. Moreover, blockade of a spe...

journal_title：Science signaling

authors： Klann E

更新日期：2009-07-21 00:00:00

abstract：:Ectodomain shedding mediated by tumor necrosis factor-α (TNF-α)-converting enzyme [TACE; also known as ADAM17 (a disintegrin and metalloproteinase 17)] provides an important switch in regulating cell proliferation, inflammation, and cancer progression. TACE-mediated ectodomain cleavage is activated by signaling of the...

journal_title：Science signaling

authors： Xu P,Liu J,Sakaki-Yumoto M,Derynck R

更新日期：2012-05-01 00:00:00

abstract：:Understanding the complex dynamics of growth factor signaling requires both mechanistic and kinetic information. Although signaling dynamics have been studied for pathways downstream of receptor tyrosine kinases and G protein (heterotrimeric guanine nucleotide-binding protein)-coupled receptors, they have not been inv...

journal_title：Science signaling

authors： Vizán P,Miller DS,Gori I,Das D,Schmierer B,Hill CS

更新日期：2013-12-10 00:00:00

abstract：:The TRAF [tumor necrosis factor receptor-associated factor] family of cytoplasmic adaptor proteins link cell-surface receptors to intracellular signaling pathways that regulate innate and adaptive immune responses. In response to activation of RIG-I (retinoic acid-inducible gene I), a component of a pattern recognitio...

journal_title：Science signaling

authors： Zhang P,Reichardt A,Liang H,Aliyari R,Cheng D,Wang Y,Xu F,Cheng G,Liu Y

更新日期：2012-11-13 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：:Jiang et al. (Research Article, 11 October 2011, DOI: 10.1126/scisignal.2002152) used a combined experimental and computational modeling approach to study the dynamic response behavior of covalent modification cycles in the presence of downstream targets ("loads"). Despite remarkable agreement between experiments and ...

journal_title：Science signaling

authors： Straube R

更新日期：2012-01-03 00:00:00

abstract：:Cyclic-di-GMP (c-di-GMP) is a bacterial second messenger that transduces internal and external signals and regulates bacterial motility and biofilm formation. Some organisms encode more than 100 c-di-GMP-modulating enzymes, but only for a few has a signal been defined that modulates their activity. We developed and ap...

journal_title：Science signaling

authors： Mills E,Petersen E,Kulasekara BR,Miller SI

更新日期：2015-06-09 00:00:00