Abstract:
:The Notch signaling pathway is essential for many aspects of development, cell fate determination, and tissue homeostasis. Notch signaling can be modulated by posttranslational modifications to the Notch receptor, which are known to alter both ligand binding and receptor activation. We have modified the ligand-binding region (EGF domains 11-13) of human Notch1 (hN1) with O-fucose and O-glucose glycans and shown by flow cytometry and surface plasmon resonance that the Fringe-catalyzed addition of GlcNAc to the O-fucose at T466 in EGF12 substantially increases binding to Jagged1 and Delta-like 1 (DLL1) ligands. We have subsequently determined the crystal structures of EGF domains 11-13 of hN1 modified with either the O-fucose monosaccharide or the GlcNAc-fucose disaccharide at T466 of EGF12 and observed no change in backbone structure for each variant. Collectively, these data demonstrate a role for GlcNAc in modulating the ligand-binding site in hN1 EGF12, resulting in an increased affinity of this region for ligands Jagged1 and DLL1. We propose that this finding explains the Fringe-catalyzed enhancement of Notch-Delta signaling observed in flies and humans, but suggest that the inhibitory effect of Fringe on Jagged/Serrate mediated signaling involves other regions of Notch.
journal_name
Proc Natl Acad Sci U S Aauthors
Taylor P,Takeuchi H,Sheppard D,Chillakuri C,Lea SM,Haltiwanger RS,Handford PAdoi
10.1073/pnas.1319683111subject
Has Abstractpub_date
2014-05-20 00:00:00pages
7290-5issue
20eissn
0027-8424issn
1091-6490pii
1319683111journal_volume
111pub_type
杂志文章abstract::We report on label-free imaging, detection, and mass/size measurement of single viral particles in solution by high-resolution surface plasmon resonance microscopy. Diffraction of propagating plasmon waves along a metal surface by the viral particles creates images of the individual particles, which allow us to detect...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1005264107
更新日期:2010-09-14 00:00:00
abstract::We report a measurement of the transverse momentum correlation between two photons by detecting only one of them. Our method uses two identical sources in an arrangement in which the phenomenon of induced coherence without induced emission is observed. In this way, we produce an interference pattern in the superpositi...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1620979114
更新日期:2017-02-14 00:00:00
abstract::Human T lymphocytes were shown to proliferate in response to tetanus toxoid antigen only in the presence of macrophages. This response was inhibited by anti-DRw but not by anti-HLA (A and B loci) antisera added to the cultures and by pretreatment of macrophages but not of T cells with anti-DRw antisera and complement....
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.76.8.4038
更新日期:1979-08-01 00:00:00
abstract::Ca channel currents were studied in freshly dispersed bovine adrenal glomerulosa cells to better understand the control of aldosterone secretion by extracellular K concentration (Ko) and angiotensin II (AII). The whole-cell variation of the patch voltage clamp technique was used. Two types of Ca channels were found. O...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.85.7.2412
更新日期:1988-04-01 00:00:00
abstract::We report here the biologically active conformation of acetylcholine when bound to the high-affinity state of the receptor from Torpedo californica. The acetylcholine conformation was determined in the free and bound states by proton NMR two-dimensional nuclear Overhauser effects. In agreement with x-ray crystallograp...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.85.18.6721
更新日期:1988-09-01 00:00:00
abstract::A flexible finite difference method is described that gives approximate solutions of linear elliptic partial differential equations, Lu = G, subject to general linear boundary conditions. The method gives high-order accuracy. The values of the unknown approximation function U are determined at mesh points by solving a...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.75.6.2541
更新日期:1978-06-01 00:00:00
abstract::We develop a potential landscape approach to quantitatively describe experimental data from a fibroblast cell line that exhibits a wide range of GFP expression levels under the control of the promoter for tenascin-C. Time-lapse live-cell microscopy provides data about short-term fluctuations in promoter activity, and ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1207544109
更新日期:2012-11-20 00:00:00
abstract::Reactive oxygen species, the by-products of oxidative energy metabolism, are considered a main proximate cause of aging. Accordingly, overexpression of the enzyme Cu-Zn superoxide dismutase 1 (SOD1) can lengthen lifespan of Drosophila melanogaster in the laboratory. However, the role of SOD1 as a main determinant of l...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0400222101
更新日期:2004-03-09 00:00:00
abstract::The VX2 carcinoma-bearing rabbit is an animal model for tumor-induced hypercalcemia, thought to be due to increased bone destruction effected by prostaglandin E2. The present experiments suggest that the pathophysiology of the hypercalcemia differs from that previously proposed. Tumor was transplanted intramuscularly ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.79.2.640
更新日期:1982-01-01 00:00:00
abstract::We resolve the 3D trajectory and the orientation of individual cells for extended times, using a digital tracking technique combined with 3D reconstructions. We have used this technique to study the motility of the uniflagellated bacterium Caulobacter crescentus and have found that each cell displays two distinct mode...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1407636111
更新日期:2014-08-05 00:00:00
abstract::Cellular DNA and RNA were simultaneously quantitated in individual cells of cycling and quiescent populations by flow cytometry. Based on differences in RNA content, two distinct subcompartments, G1A and G1B, were recognized in the G1 phase of exponentially growing cells. After mitosis, cells reside in the low-RNA, G1...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.77.11.6696
更新日期:1980-11-01 00:00:00
abstract::The proteinase-activated receptor 2 (PAR-2) is a member of a family of G protein-coupled receptors for proteases. Proteases cleave PARs within the extracellular N-terminal domains to expose tethered ligands that bind to and activate the cleaved receptors. PAR-2 is highly expressed in colon in epithelial and neuronal e...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.241377298
更新日期:2001-11-20 00:00:00
abstract::The heptadecapeptide orphanin FQ (OFQ) is a recently discovered neuropeptide that exhibits structural features reminiscent of the opioid peptides and that is an endogenous ligand to a G protein-coupled receptor sequentially related to the opioid receptors. We have cloned both the human and rat cDNAs encoding the OFQ p...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.93.16.8677
更新日期:1996-08-06 00:00:00
abstract::The nuclear lamina is a network of structural filaments, the A and B type lamins, located at the nuclear envelope and throughout the nucleus. Lamin filaments provide the nucleus with mechanical stability and support many basic activities, including gene regulation. Mutations in LMNA, the gene encoding A type lamins, c...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0601058103
更新日期:2006-07-05 00:00:00
abstract::Contingency models of feeding compare the energy per unit time gained from utilizing a resource unit of a particular kind (food types, habitat patches, time periods) against that energy/time expected if the unit is skipped. Optimally, an animal should reject the particular unit if and only if the former energy/time is...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.71.10.4169
更新日期:1974-10-01 00:00:00
abstract::The endometrial epithelium of the uterus regenerates periodically. The cellular source of newly regenerated endometrial epithelia during a mouse estrous cycle or a human menstrual cycle is presently unknown. Here, I have used single-cell lineage tracing in the whole mouse uterus to demonstrate that epithelial stem cel...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1814597116
更新日期:2019-04-02 00:00:00
abstract::Urbanization represents an extreme transformation of more natural systems. Populations of most species decline or disappear with urbanization, and yet some species persist and even thrive in cities. What determines which species persist or thrive in urban habitats? Direct competitive interactions among species can inf...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1809317115
更新日期:2018-12-04 00:00:00
abstract::We previously have identified a subpopulation of contact-insensitive (CS-) cells which lacks density-dependent inhibition of cell division in primary and low-passage cultures of Syrian hamster embryonic (SHE) fibroblastic cells. Further, we have shown that the proportion of these CS- cells declines as a result of the ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.82.15.5005
更新日期:1985-08-01 00:00:00
abstract::Markov chain Monte Carlo (MCMC) or the Metropolis-Hastings algorithm is a simulation algorithm that has made modern Bayesian statistical inference possible. Nevertheless, the efficiency of different Metropolis-Hastings proposal kernels has rarely been studied except for the Gaussian proposal. Here we propose a unique ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1311790110
更新日期:2013-11-26 00:00:00
abstract::The two large cytoplasmic domains (C1 and C2) of adenylyl cyclases (AC), when expressed separately and mixed together, reconstitute enzyme activity that can be regulated by various modulators. Therefore, we have used the C1 or its C1a subdomain and C2 regions from type I AC (ACI) and type V AC (ACV) to identify the re...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.96.17.9551
更新日期:1999-08-17 00:00:00
abstract::We have investigated the minimum extent of DNA sequence required for the attachment site of bacteriophage lambda to function in integrative recombination. A DNA fragment carrying the phage attachment site (attP) of bacteriophage lambda was trimmed, recloned, and tested for recombination proficiency. In order to recomb...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.77.6.3220
更新日期:1980-06-01 00:00:00
abstract::Tregs are essential for maintaining peripheral tolerance, and thus targeting these cells may aid in the treatment of autoimmunity and cancer by enhancing or reducing suppressive functions, respectively. Before these cells can be harnessed for therapeutic purposes, it is necessary to understand how they maintain tolera...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1605849113
更新日期:2016-08-09 00:00:00
abstract::Antisense RNA to the 27/32-kDa rat liver gap junction (GJ) protein was used to explore the role of GJs in preimplantation embryos. When all blastomeres of two- and four-cell embryos were injected with GJ antisense RNA, the percentage of embryos compacted at 60 hr of development was reduced to less than 20%, while 90% ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.86.14.5444
更新日期:1989-07-01 00:00:00
abstract::Antigen.antibody complexes (Ag.Ab) prepared from (125)I-labeled bovine serum albumin and guinea pig anti-albumin were incubated at 37 degrees C for 30 min with normal human serum diluted optimally for binding (1:16) and then with autologous erythrocytes (RBC). After washing, RBC-bearing antigen.antibody.complement com...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.79.16.5047
更新日期:1982-08-01 00:00:00
abstract::Superficial cells from early amphibian embryos display regional specializations of their cell surfaces. That portion of the plasma membrane facing the perivitelline space (apical surface) is nonadhesive, whereas, in the same cell, the lateral and basal portions of the plasma membrane will adhere to other cells. These ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.77.6.3460
更新日期:1980-06-01 00:00:00
abstract::Phytochrome is the photoreceptor that controls red light-mediated morphogenesis in higher plants. It exists in two photointerconvertible forms, a red light-absorbing form, Pr, and a far-red light-absorbing form, Pfr. Because photoconversion of Pr to Pfr by a brief light pulse decreases the in vivo half-life of this ch...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.84.2.359
更新日期:1987-01-01 00:00:00
abstract::cDNA fragments of the homologues of the Drosophila head homeotic genes labial (lab), proboscipedia (pb), and Deformed (Dfd) have been isolated from the crustacean Porcellio scaber. Because the accumulation domains of the head homeotic complex (Hox) genes had not been previously reported for crustaceans, we studied the...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.96.18.10224
更新日期:1999-08-31 00:00:00
abstract::It is a long-standing proposal that localization of maternal factors in eggs can provide the basis for pattern formation in the early embryo. The localized information can be stored as RNA, one example being Vg1 RNA, which is localized exclusively to the vegetal hemisphere of Xenopus oocytes and eggs. Localization of ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.93.25.14608
更新日期:1996-12-10 00:00:00
abstract::The sustainability of irrigated agriculture in many arid and semiarid areas of the world is at risk because of a combination of several interrelated factors, including lack of fresh water, lack of drainage, the presence of high water tables, and salinization of soil and groundwater resources. Nowhere in the United Sta...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0507723102
更新日期:2005-10-25 00:00:00
abstract::Classic physiology studies dating to the 1930s demonstrate that moderate or transient glucocorticoid (GC) exposure improves muscle performance. The ergogenic properties of GCs are further evidenced by their surreptitious use as doping agents by endurance athletes and poorly understood efficacy in Duchenne muscular dys...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1512968112
更新日期:2015-12-08 00:00:00