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_name
Sci Signaljournal_title
Science signalingauthors
Best SM,Ponia SSdoi
10.1126/scisignal.aaw8549subject
Has Abstractpub_date
2019-03-19 00:00:00issue
573eissn
1945-0877issn
1937-9145pii
12/573/eaaw8549journal_volume
12pub_type
评论,杂志文章,评审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
pub_type: 杂志文章
doi:10.1126/scisignal.2002010
更新日期:2011-10-25 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
pub_type: 杂志文章
doi:10.1126/scisignal.aar2125
更新日期:2018-08-28 00:00:00
abstract::Chimeric antigen receptors (CARs) link an antigen recognition domain to intracellular signaling domains to redirect T cell specificity and function. T cells expressing CARs with CD28/CD3ζ or 4-1BB/CD3ζ signaling domains are effective at treating refractory B cell malignancies but exhibit differences in effector functi...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.aat6753
更新日期:2018-08-21 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
pub_type: 杂志文章,评审
doi:10.1126/scisignal.2002989
更新日期:2012-04-24 00:00:00
abstract::Teaching the practical aspects of signal transduction to large undergraduate classes can be challenging when there is only a finite time frame in which to engage in laboratory activities. This teaching resource describes the use of bead-based ALPHAscreen technology for a class of 300 second-year biochemistry students,...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.262tr1
更新日期:2009-03-17 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
pub_type: 杂志文章,评审
doi:10.1126/scisignal.280pe42
更新日期:2009-07-21 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
pub_type: 杂志文章
doi:10.1126/scisignal.aao5150
更新日期:2018-10-16 00:00:00
abstract::A major endpoint of the canonical Wnt signaling pathway is a change in the transcription of target genes. The transcription factors lymphoid enhancer factor (LEF) and T cell factor (TCF) serve as the main gatekeepers of these changes by selecting genes to be targeted by the transcriptional coregulator beta-catenin and...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.139pe43
更新日期:2008-09-30 00:00:00
abstract::The detection of microbes and initiation of an innate immune response occur through pattern recognition receptors (PRRs), which are critical for the production of inflammatory cytokines and activation of the cellular microbicidal machinery. In particular, the production of reactive oxygen species (ROS) by the NADPH ox...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.aac6250
更新日期:2016-02-02 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
pub_type: 杂志文章
doi:10.1126/scisignal.3119jc4
更新日期:2010-04-27 00:00:00
abstract::Multiple sclerosis (MS) is a human disease that results from autoimmune T cells targeting myelin protein that is expressed within the central nervous system. In MS, the number of FoxP3-expressing regulatory T cells (Tregs) is reduced, which facilitates the activation of autoreactive T cells. Because aspirin (acetylsal...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.aar8278
更新日期:2018-11-27 00:00:00
abstract::Toll-like receptor (TLR) signaling regulates macrophage activation and effector cytokine propagation in the constrained environment of a tissue. In macrophage populations, TLR4 stimulates the dose-dependent transcription of nuclear factor κB (NF-κB) target genes. However, using single-RNA counting, we found that indiv...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.aaf3998
更新日期:2018-07-24 00:00:00
abstract::Postsynaptic organizational protein complexes play central roles both in orchestrating synapse formation and in defining the functional properties of synaptic transmission that together shape the flow of information through neuronal networks. A key component of these organizational protein complexes is the family of s...
journal_title:Science signaling
pub_type: 杂志文章,评审
doi:10.1126/scisignal.abd8379
更新日期:2020-12-22 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
pub_type: 杂志文章
doi:10.1126/scisignal.aau4543
更新日期:2019-03-12 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
pub_type: 杂志文章
doi:10.1126/scisignal.aaf6625
更新日期:2016-10-11 00:00:00
abstract::Bone morphogenetic proteins (BMPs) and Wnts are growth factors that provide essential patterning signals for cell proliferation and differentiation. Here, we describe a molecular mechanism by which the phosphorylation state of the Drosophila transcription factor Mad determines its ability to transduce either BMP or Wi...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.2002034
更新日期:2011-10-11 00:00:00
abstract::The prevailing view has been that N-terminally truncated p53 family isoforms (ΔNp53, ΔNp63, and DNp73) predominantly counteract cell cycle arrest and apoptosis. Recent progress in the field extend these well-known functions and place these isoforms in the center of a comprehensive regulatory network controlling major ...
journal_title:Science signaling
pub_type: 杂志文章,评审
doi:10.1126/scisignal.2005699
更新日期:2014-09-30 00:00:00
abstract::The prefibrillar form of soluble amyloid-β (sAβ1-42) impairs synaptic function and is associated with the early phase of Alzheimer's disease (AD). We investigated how sAβ1-42 led to presynaptic defects using a quantum dot-based, single particle-tracking method to monitor synaptic vesicle (SV) trafficking along axons. ...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.aam8661
更新日期:2017-07-11 00:00:00
abstract::Huntington's disease (HD) is a neurodegenerative disease caused by an expansion in the huntingtin protein (also called Htt) that induces neuronal cell death with age. We found that the treatment of 12-month-old symptomatic heterozygous and homozygous zQ175 huntingtin knockin mice for 12 weeks with CTEP, a negative all...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.aan6387
更新日期:2017-12-19 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
pub_type: 杂志文章
doi:10.1126/scisignal.2000442
更新日期:2009-10-27 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
pub_type: 杂志文章,评审
doi:10.1126/scisignal.143jc2
更新日期:2008-10-28 00:00:00
abstract::Netrin-1 displays proto-oncogenic activity in several cancers, which is thought to be due to the ability of this secreted cue to stimulate survival when bound to its receptors. We showed that in contrast to full-length, secreted netrin-1, some cancer cells produced a truncated intranuclear form of netrin-1 (ΔN-netrin-...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.2002456
更新日期:2012-08-07 00:00:00
abstract::The advent of deep-sequencing techniques has revealed that mutations in G protein-coupled receptor (GPCR) signaling pathways in cancer are more prominent than was previously appreciated. An emergent theme is that cancer-associated mutations tend to cause enhanced GPCR pathway activation to favor oncogenicity. Regulato...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.aax8620
更新日期:2020-02-04 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
pub_type: 杂志文章
doi:10.1126/scisignal.2005522
更新日期:2014-09-16 00:00:00
abstract::Cross-linking of proteins by mammalian transglutaminases (TGs) plays important roles in physiological phenomena such as blood coagulation and skin formation. We show that Drosophila TG suppressed innate immune signaling in the gut. RNA interference (RNAi) directed against TG reduced the life span of flies reared under...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.2003970
更新日期:2013-07-23 00:00:00
abstract::MicroRNAs (miRNAs) are small noncoding RNAs that suppress the abundance of partially complementary mRNAs and inhibit their translation. Each miRNA can regulate hundreds of mRNAs, sometimes strongly but often weakly, to mediate a diverse array of biological functions, including proliferation, cell signaling, differenti...
journal_title:Science signaling
pub_type: 杂志文章,评审
doi:10.1126/scisignal.2005825
更新日期:2015-03-17 00:00:00
abstract::Inositol pyrophosphates are highly energetic inositol polyphosphate molecules present in organisms from slime molds and yeast to mammals. Distinct classes of enzymes generate different forms of inositol pyrophosphates. The biosynthesis of these substances principally involves phosphorylation of inositol hexakisphospha...
journal_title:Science signaling
pub_type: 杂志文章,评审
doi:10.1126/scisignal.2001958
更新日期:2011-08-23 00:00:00
abstract::Interleukin-2 (IL-2)-inducible T cell kinase (ITK) mediates T cell receptor (TCR) signaling primarily to stimulate the production of cytokines, such as IL-4, IL-5, and IL-13, from T helper 2 (TH2) cells. Compared to wild-type mice, ITK knockout mice are resistant to asthma and exhibit reduced lung inflammation and dec...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.aab0949
更新日期:2015-12-01 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
pub_type: 杂志文章
doi:10.1126/scisignal.2004657
更新日期:2013-10-15 00:00:00
abstract::One reported function of the tumor suppressor p19(Arf) is to stabilize p53, providing a critical checkpoint in the response to oncogenic insults. Acute loss of Pten leads to an increase in the abundance of p19(Arf), p53, and p21 proteins as part of a fail-safe senescence response. Here, we report that loss of p19(Arf)...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.2000053
更新日期:2009-08-18 00:00:00