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 from the host immune system, whereas MUC1 is less abundant in certain other cells-for example, in trophoblasts and hematopoietic cells. Most of the functions of MUC1 depend upon its large, extracellular ectodomain. Nonetheless, a series of studies have demonstrated a surprisingly diverse role for the small, highly conserved cytoplasmic domain of MUC1 in intracellular signaling. These intracellular activities have potential roles in the physiology of both malignant and nonmalignant cells.
journal_name
Sci Signaljournal_title
Science signalingauthors
Carson DDdoi
10.1126/scisignal.127pe35subject
Has Abstractpub_date
2008-07-08 00:00:00pages
pe35issue
27eissn
1945-0877issn
1937-9145pii
scisignal.127pe35journal_volume
1pub_type
杂志文章,评审abstract::ONC201 (also called TIC10) is a small molecule that inactivates the cell proliferation- and cell survival-promoting kinases Akt and ERK and induces cell death through the proapoptotic protein TRAIL. ONC201 is currently in early-phase clinical testing for various malignancies. We found through gene expression and prote...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.aac4374
更新日期:2016-02-16 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
pub_type: 杂志文章,评审
doi:10.1126/scisignal.aaa0974
更新日期:2015-04-28 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
pub_type: 杂志文章
doi:10.1126/scisignal.2005301
更新日期:2014-12-23 00:00:00
abstract::Deoxyhypusine synthase (DHPS) uses the polyamine spermidine to catalyze the hypusine modification of the mRNA translation factor eIF5A and promotes oncogenesis through poorly defined mechanisms. Because germline deletion of Dhps is embryonically lethal, its role in normal postnatal cellular function in vivo remains un...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.aax0715
更新日期:2019-12-03 00:00:00
abstract::By regulating gene expression, microRNAs (miRNAs) play pivotal roles in physiological and pathological processes. However, the regulation of miRNAs is elusive. miR-192 is a key regulator of renal fibrosis and hypertrophy in diabetic nephropathy. Natarajan et al. showed that the miR-192 gene contains an upstream region...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.2004299
更新日期:2013-06-04 00:00:00
abstract::When we are frightened, our hearts beat more rapidly and forcefully so we can fight more intensely or run away faster. This fight-or-flight response is triggered by the release of norepinephrine from neurons of the sympathetic nervous system. Norepinephrine activates the classic β-adrenergic receptor-heterotrimeric G(...
journal_title:Science signaling
pub_type: 评论,杂志文章
doi:10.1126/scisignal.3141pe33
更新日期:2010-09-28 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
pub_type: 杂志文章,评审
doi:10.1126/scisignal.290re7
更新日期:2009-09-29 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::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
pub_type: 杂志文章
doi:10.1126/scisignal.2005703
更新日期:2014-09-09 00:00:00
abstract::Double knockout of PTEN and LKB1-genes encoding phosphatase and tensin homolog and liver kinase B1, respectively-leads to the spontaneous development of cancer in mice. PTEN converts phosphatidylinositol (3,4,5)-trisphosphate (PIP3) to phosphatidylinositol (4,5)-bisphosphate (PIP2), whereas LKB1 activates the 5' adeno...
journal_title:Science signaling
pub_type: 杂志文章,评审
doi:10.1126/scisignal.aac8321
更新日期:2015-09-01 00:00:00
abstract::Adenosine 5'-diphosphate (ADP)-ribosylation is a protein posttranslational modification that is catalyzed by ADP-ribosyltransferases (ARTs), using nicotinamide adenine dinucleotide (NAD(+)) as a substrate. Mono-ribosylation can be extended into polymers of ADP-ribose (PAR). Poly(ADP-ribosyl)polymerase (PARP) 1, the be...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.2001645
更新日期:2011-05-24 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
pub_type: 杂志文章
doi:10.1126/scisignal.2002049
更新日期:2011-09-27 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::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::Mutations in ERBB2, the gene encoding epidermal growth factor receptor (EGFR) family member HER2, are common in and drive the growth of "HER2-negative" (not ERBB2 amplified) tumors but are rare in "HER2-positive" (ERBB2 amplified) breast cancer. We analyzed DNA-sequencing data from HER2-positive patients and used cell...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.aat9773
更新日期:2018-10-09 00:00:00
abstract::Most metazoans have at least some ability to regenerate damaged cells and tissues, although the regenerative capacity varies depending on the species, organ, or developmental stage. Cell replacement and regeneration occur in two contexts: renewal of spent cells during tissue homeostasis (homeostatic growth), and in re...
journal_title:Science signaling
pub_type: 杂志文章,评审
doi:10.1126/scisignal.3145re8
更新日期:2010-10-26 00:00:00
abstract::The differentiation of fibroblasts into a transient population of highly activated, extracellular matrix (ECM)-producing myofibroblasts at sites of tissue injury is critical for normal tissue repair. Excessive myofibroblast accumulation and persistence, often as a result of a failure to undergo apoptosis when tissue r...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.aav3048
更新日期:2019-05-21 00:00:00
abstract::The V600E mutation in the kinase BRAF is frequently detected in melanomas and results in constitutive activation of BRAF, which then promotes cell proliferation by the mitogen-activated protein kinase signaling pathway. Although the BRAFV600E kinase inhibitor vemurafenib has remarkable antitumor activity in patients w...
journal_title:Science signaling
pub_type: 临床试验,杂志文章
doi:10.1126/scisignal.2003057
更新日期:2013-01-29 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
pub_type: 杂志文章
doi:10.1126/scisignal.aaf5642
更新日期:2016-08-23 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::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
pub_type: 杂志文章
doi:10.1126/scisignal.2002179
更新日期:2011-12-20 00:00:00
abstract::Chemoattractants induce cell migration through the activation of a distinct family of structurally related heterotrimeric guanine nucleotide-binding protein (G protein)-coupled receptors. Over the past few years, several receptors in this family have been identified that recognize different classes of chemoattractants...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.259pe10
更新日期:2009-02-24 00:00:00
abstract::The PAR-1-MARK pathway controls cell polarity through the phosphorylation of microtubule-associated proteins. Rho-Rac guanine nucleotide exchange factor 2 (ARHGEF2), which activates Ras homolog family member A (RHOA), is anchored to the microtubule network and sequestered in an inhibited state through binding to dynei...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.aan3286
更新日期:2017-10-31 00:00:00
abstract::Clinical response to chimeric antigen receptor (CAR) T cell therapy is correlated with CAR T cell persistence, especially for CAR T cells that target CD19+ hematologic malignancies. 4-1BB-costimulated CAR (BBζ) T cells exhibit longer persistence after adoptive transfer than do CD28-costimulated CAR (28ζ) T cells. 4-1B...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.aay8248
更新日期:2020-03-31 00:00:00
abstract::Cellular proliferation, differentiation, and morphogenesis are shaped by multiple signaling cascades, and their dysregulation plays an integral role in cancer progression. Three cascades that contribute to oncogenic potential are those mediated by Wnt proteins and the receptor Frizzled (FZD), growth factor receptor ty...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.aao4220
更新日期:2018-02-27 00:00:00
abstract::The hexosamine biosynthetic pathway, whose end product is UDP-N acetylglucosamine (UDP-GlcNAc), lies at the base of cellular glycosylation pathways, including glycosylation of lipids, formation of heparin sulfated proteoglycans, and N- and O-linked glycosylation of proteins. Forward genetic studies in Drosophila have ...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.2002789
更新日期:2012-01-17 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
pub_type: 杂志文章
doi:10.1126/scisignal.2001821
更新日期:2011-10-04 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::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::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
pub_type: 杂志文章
doi:10.1126/scisignal.2002258
更新日期:2011-08-09 00:00:00