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 antimicrobial responses to the dose of pathogen-associated molecular cues. This finding stemmed from analysis of cell-to-cell variability and computational modeling of time integration between signaling and transcriptional responses. Ultimately, such quantitative approaches challenge the oft-assumed time separation of "fast" signal transduction followed by "slow" gene expression, and they provide a better understanding of complex biological regulation over long time scales.
journal_name
Sci Signaljournal_title
Science signalingauthors
Tkach KE,Oyler JE,Altan-Bonnet Gdoi
10.1126/scisignal.2005108subject
Has Abstractpub_date
2014-02-18 00:00:00pages
pe5issue
313eissn
1945-0877issn
1937-9145pii
7/313/pe5journal_volume
7pub_type
杂志文章,评审abstract::Type I interferons (IFNs), including various IFN-α isoforms and IFN-β, are a family of homologous, multifunctional cytokines. IFNs activate different cellular responses by binding to a common receptor that consists of two subunits, IFNAR1 and IFNAR2. In addition to stimulating antiviral responses, they also inhibit ce...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.2004998
更新日期:2014-05-27 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
pub_type: 评论,杂志文章,评审
doi:10.1126/scisignal.aay8960
更新日期:2019-10-15 00:00:00
abstract::The activation of T cells requires the guanine nucleotide exchange factor VAV1. Using mice in which a tag for affinity purification was attached to endogenous VAV1 molecules, we analyzed by quantitative mass spectrometry the signaling complex that assembles around activated VAV1. Fifty VAV1-binding partners were ident...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.aar3083
更新日期:2018-07-10 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
pub_type: 杂志文章
doi:10.1126/scisignal.2001993
更新日期:2011-11-08 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::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
pub_type: 评论,信件
doi:10.1126/scisignal.2002699
更新日期:2012-01-03 00:00:00
abstract::Insulin receptor substrate 2 (IRS2) is an adaptor protein that becomes tyrosine-phosphorylated in response to the cytokines interleukin-4 (IL-4) and IL-13, which results in activation of the phosphoinositide 3-kinase (PI3K)-Akt pathway. IL-4 and IL-13 contribute to allergic lung inflammation. To examine the role of IR...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.aad6724
更新日期:2016-06-21 00:00:00
abstract::Birth defects of the heart and face are common, and most have no known genetic cause, suggesting a role for environmental factors. Maternal fever during the first trimester is an environmental risk factor linked to these defects. Neural crest cells are precursor populations essential to the development of both at-risk...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.aal4055
更新日期:2017-10-10 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
pub_type: 杂志文章
doi:10.1126/scisignal.aan5598
更新日期:2018-01-09 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
pub_type: 杂志文章
doi:10.1126/scisignal.2005052
更新日期:2014-07-08 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
pub_type: 杂志文章
doi:10.1126/scisignal.aaa5622
更新日期:2015-06-02 00:00:00
abstract::The guanosine triphosphatases of the Rho and Rac subfamilies regulate protumorigenic pathways and are activated by guanine nucleotide exchange factors (Rho GEFs), which could be potential targets for anticancer therapies. We report that two Rho GEFs, Vav2 and Vav3, play synergistic roles in breast cancer by sustaining...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.2002962
更新日期:2012-10-02 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
pub_type: 杂志文章
doi:10.1126/scisignal.2002466
更新日期:2012-02-14 00:00:00
abstract::New therapeutic approaches for chronic inflammatory diseases such as inflammatory bowel disease, rheumatoid arthritis, and psoriasis are needed because current treatments are often suboptimal in terms of both efficacy and the risks of serious adverse events. Inhibitor of apoptosis proteins (IAPs) are E3 ubiquitin liga...
journal_title:Science signaling
pub_type: 杂志文章,评审
doi:10.1126/scisignal.aax8295
更新日期:2020-02-18 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::Frizzleds (FZDs) are a group of seven transmembrane-spanning (7TM) receptors that belong to class F of the G protein-coupled receptor (GPCR) superfamily. FZDs bind WNT proteins to stimulate diverse signaling cascades involved in embryonic development, stem cell regulation, and adult tissue homeostasis. Frizzled 5 (FZD...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.aar5536
更新日期:2018-12-04 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
pub_type: 杂志文章,评审
doi:10.1126/scisignal.aaw8715
更新日期:2019-04-16 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
pub_type: 杂志文章,评审
doi:10.1126/scisignal.2002165
更新日期:2011-10-18 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
pub_type: 杂志文章
doi:10.1126/scisignal.aaf6209
更新日期:2016-05-10 00:00:00
abstract::Intracranial aneurysms are common but are generally untreated, and their rupture can lead to subarachnoid hemorrhage. Because of the poor prognosis associated with subarachnoid hemorrhage, preventing the progression of intracranial aneurysms is critically important. Intracranial aneurysms are caused by chronic inflamm...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.aah6037
更新日期:2017-02-07 00:00:00
abstract::The cytokine interleukin-22 (IL-22), which is a member of the IL-10 family, is produced exclusively by immune cells and activates signal transducer and activator of transcription 3 (STAT3) in nonimmune cells, such as hepatocytes, keratinocytes, and colonic epithelial cells, to drive various processes central to tissue...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.aad9887
更新日期:2016-09-27 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
pub_type:
doi:10.1126/scisignal.aaz0961
更新日期:2019-09-17 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::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::The European Molecular Biology Organization (EMBO) meeting Visualizing Immune System Complexity, held in January 2009, covered multiple scales, from imaging single molecules to imaging whole animals. In addition to experimental details, there was an emphasis on modeling both for data analysis and as a predictive tool ...
journal_title:Science signaling
pub_type:
doi:10.1126/scisignal.266mr4
更新日期:2009-04-14 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
pub_type: 杂志文章,评审
doi:10.1126/scisignal.3110pe7
更新日期:2010-02-23 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
pub_type: 杂志文章
doi:10.1126/scisignal.2004557
更新日期:2014-02-04 00:00:00
abstract::Plants and animals produce reactive oxygen species (ROS) in response to infection. In plants, ROS not only activate defense responses and promote cell death to limit the spread of pathogens but also restrict the amount of cell death in response to pathogen recognition. Plants also use hormones, such as salicylic acid,...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.2004777
更新日期:2014-04-08 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
pub_type:
doi:10.1126/scisignal.268pt3
更新日期:2009-04-28 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