Subtle modifications to oxytocin produce ligands that retain potency and improved selectivity across species.

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：:Store-operated Ca2+ entry (SOCE) channels are highly selective Ca2+ channels activated by the endoplasmic reticulum (ER) sensors STIM1 and STIM2. Their direct interaction with the pore-forming plasma membrane ORAI proteins (ORAI1, ORAI2, and ORAI3) leads to sustained Ca2+ fluxes that are critical for many cellular fun...

journal_title：Science signaling

authors： Eckstein M,Vaeth M,Aulestia FJ,Costiniti V,Kassam SN,Bromage TG,Pedersen P,Issekutz T,Idaghdour Y,Moursi AM,Feske S,Lacruz RS

更新日期：2019-04-23 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 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：:Over the last 50 years, the posttranslational modification (PTM) of proteins has emerged as a central mechanism for cells to regulate metabolism, growth, differentiation, cell-cell interactions, and immune responses. By influencing protein structure and function, PTM leads to a multiplication of proteome diversity. Re...

journal_title：Science signaling

authors： Rudolph TK,Freeman BA

更新日期：2009-09-29 00:00:00

abstract：:We previously developed a web tool, Transcriptomine, to explore expression profiling data sets involving small-molecule or genetic manipulations of nuclear receptor signaling pathways. We describe advances in biocuration, query interface design, and data visualization that enhance the discovery of uncharacterized biol...

journal_title：Science signaling

authors： Becnel LB,Ochsner SA,Darlington YF,McOwiti A,Kankanamge WH,Dehart M,Naumov A,McKenna NJ

更新日期：2017-04-25 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：:Spontaneous neural differentiation of embryonic stem cells is induced by Noggin-mediated inhibition of bone morphogenetic protein 4 (BMP4) signaling. RhoA is a guanosine triphosphatase (GTPase) that regulates cytoskeletal dynamics and gene expression, both of which control stem cell fate. We found that disruption of S...

journal_title：Science signaling

authors： Yang J,Wu C,Stefanescu I,Jakobsson L,Chervoneva I,Horowitz A

更新日期：2016-07-26 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：:An often-asked question is, Why are there so many different transporters in a cell to take up a particular substrate? At least part of the answer comes from work on the possible competitive advantage of dual-transporter systems. In such systems, low-affinity transporters function when a nutrient is plentiful in the en...

journal_title：Science signaling

authors： Eide DJ

更新日期：2012-02-07 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：:TLR4-stimulated B cell activation is mediated by the tyrosine kinase Syk and depends on the B cell receptor. ...

journal_title：Science signaling

authors： Foley JF

更新日期：2017-05-23 00:00:00

abstract：:The accumulation of damaged or excess proteins and organelles is a defining feature of metabolic disease in nearly every tissue. Thus, a central challenge in maintaining metabolic homeostasis is the identification, sequestration, and degradation of these cellular components, including protein aggregates, mitochondria,...

journal_title：Science signaling

authors： Evans TD,Sergin I,Zhang X,Razani B

更新日期：2017-02-28 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：:Extracellular hyperosmolarity, or osmotic stress, generally caused by differences in salt and macromolecule concentrations across the plasma membrane, occurs in lymphoid organs and at inflammatory sites. The response of immune cells to osmotic stress is regulated by nuclear factor of activated T cells 5 (NFAT5), a tra...

journal_title：Science signaling

authors： Kino T,Takatori H,Manoli I,Wang Y,Tiulpakov A,Blackman MR,Su YA,Chrousos GP,DeCherney AH,Segars JH

更新日期：2009-02-10 00:00:00

abstract：:Calcium/calmodulin-dependent protein kinase II (CaMKII) plays a central role in Ca2+ signaling throughout the body. In the hippocampus, CaMKII is required for learning and memory. Vertebrate genomes encode four CaMKII homologs: CaMKIIα, CaMKIIβ, CaMKIIγ, and CaMKIIδ. All CaMKIIs consist of a kinase domain, a regulator...

journal_title：Science signaling

authors： Sloutsky R,Dziedzic N,Dunn MJ,Bates RM,Torres-Ocampo AP,Boopathy S,Page B,Weeks JG,Chao LH,Stratton MM

更新日期：2020-07-21 00:00:00

abstract：:The organization and renewal capacity of teeth vary greatly among vertebrates. Mammals have only one row of teeth that are renewed at most once, whereas many nonmammalian species have multirowed dentitions and show remarkable capacity to replace their teeth throughout life. Although knowledge on the genetic basis of t...

journal_title：Science signaling

authors： Mikkola ML

更新日期：2009-08-25 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：:A central component of receptor-evoked Ca(2+) signaling is store-operated Ca(2+) entry (SOCE), which is activated by the assembly of STIM1-Orai1 channels in endoplasmic reticulum (ER) and plasma membrane (PM) (ER-PM) junctions in response to depletion of ER Ca(2+). We report that STIM2 enhances agonist-mediated activa...

journal_title：Science signaling

authors： Ong HL,de Souza LB,Zheng C,Cheng KT,Liu X,Goldsmith CM,Feske S,Ambudkar IS

更新日期：2015-01-13 00:00:00

abstract：:Oxygen sensing by the carotid body is essential in vertebrates to adapt to reduced arterial oxygen tension. In this issue of Science Signaling, Yuan et al. report an intricate signaling system to transduce a physical parameter--oxygen tension--into a biological cellular signal (neural discharge) through changes in the...

journal_title：Science signaling

authors： Fandrey J

更新日期：2015-04-21 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：: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：: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：: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：:A system-wide analysis of cell signaling requires detecting and quantifying many different proteins and their posttranslational modification states in the same cellular sample. Here, we present Protocols for two miniaturized, array-based methods, one of which provides detailed information on a central signaling protei...

journal_title：Science signaling

authors： Luckert K,Gujral TS,Chan M,Sevecka M,Joos TO,Sorger PK,Macbeath G,Pötz O

更新日期：2012-01-10 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：:Signaling proteins evolved diverse interactions to provide specificity for distinct stimuli. Signaling complexity in the G protein (heterotrimeric guanosine triphosphate-binding protein) network was achieved in animals through subunit duplication and incremental evolution. By combining comprehensive and quantitative p...

journal_title：Science signaling

authors： Urano D,Maruta N,Trusov Y,Stoian R,Wu Q,Liang Y,Jaiswal DK,Thung L,Jackson D,Botella JR,Jones AM

更新日期：2016-09-20 00:00:00

abstract：:Toll-like receptors (TLRs) recognize pathogen-associated molecular patterns (PAMPs) and stimulate the innate immune response through the production of cytokines. The innate immune response depends on the timing of encountering PAMPs, suggesting a short-term "memory." In particular, activation of TLR3 appears to prime ...

journal_title：Science signaling

authors： Liu B,Liu Q,Yang L,Palaniappan SK,Bahar I,Thiagarajan PS,Ding JL

更新日期：2016-07-12 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：: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