Signal transduction by activated mNotch: importance of proteolytic processing and its regulation by the extracellular domain.

Abstract:

:Previous studies imply that the intracellular domain of Notch1 must translocate to the nucleus for its activity. In this study, we demonstrate that a mNotch1 mutant protein that lacks its extracellular domain but retains its membrane-spanning region becomes proteolytically processed on its intracellular surface and, as a result, the activated intracellular domain (mNotchIC) is released and can move to the nucleus. Proteolytic cleavage at an intracellular site is blocked by protease inhibitors. Intracellular cleavage is not seen in cells transfected with an inactive variant, which includes the extracellular lin-Notch-glp repeats. Collectively, the studies presented here support the model that mNotch1 is proteolytically processed and the cleavage product is translocated to the nucleus for mNotch1 signal transduction.

authors

Kopan R,Schroeter EH,Weintraub H,Nye JS

doi

10.1073/pnas.93.4.1683

subject

Has Abstract

pub_date

1996-02-20 00:00:00

pages

1683-8

issue

4

eissn

0027-8424

issn

1091-6490

journal_volume

93

pub_type

杂志文章
  • Tyrosine kinase inhibitors reverse type 1 diabetes in nonobese diabetic mice.

    abstract::The recent development of small-molecule tyrosine kinase (TK) inhibitors offers increasing opportunities for the treatment of autoimmune diseases. In this study, we investigated the potential of this new class of drugs to treat and cure type 1 diabetes (T1D) in the NOD mouse. Treatment of prediabetic and new onset dia...

    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.0810246105

    authors: Louvet C,Szot GL,Lang J,Lee MR,Martinier N,Bollag G,Zhu S,Weiss A,Bluestone JA

    更新日期:2008-12-02 00:00:00

  • Lysosome inhibition sensitizes pancreatic cancer to replication stress by aspartate depletion.

    abstract::Functional lysosomes mediate autophagy and macropinocytosis for nutrient acquisition. Pancreatic ductal adenocarcinoma (PDAC) tumors exhibit high basal lysosomal activity, and inhibition of lysosome function suppresses PDAC cell proliferation and tumor growth. However, the codependencies induced by lysosomal inhibitio...

    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.1812410116

    authors: Elliott IA,Dann AM,Xu S,Kim SS,Abt ER,Kim W,Poddar S,Moore A,Zhou L,Williams JL,Capri JR,Ghukasyan R,Matsumura C,Tucker DA,Armstrong WR,Cabebe AE,Wu N,Li L,Le TM,Radu CG,Donahue TR

    更新日期:2019-04-02 00:00:00

  • Integration of light and abscisic acid signaling during seed germination and early seedling development.

    abstract::Seed germination is regulated by endogenous hormonal cues and external environmental stimuli such as water, low temperature, and light. After germination, the young seedling must rapidly establish its root system and the photoautotrophic capability appropriate to its surrounding environment. Light and the phytohormone...

    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.0710778105

    authors: Chen H,Zhang J,Neff MM,Hong SW,Zhang H,Deng XW,Xiong L

    更新日期:2008-03-18 00:00:00

  • An inherited p53 mutation that contributes in a tissue-specific manner to pediatric adrenal cortical carcinoma.

    abstract::The incidence of pediatric adrenal cortical carcinoma (ACC) in southern Brazil is 10-15 times higher than that of pediatric ACC worldwide. Because childhood ACC is associated with Li-Fraumeni syndrome, we examined the cancer history and p53 status of 36 Brazilian patients and their families. Remarkably, 35 of 36 patie...

    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.161479898

    authors: Ribeiro RC,Sandrini F,Figueiredo B,Zambetti GP,Michalkiewicz E,Lafferty AR,DeLacerda L,Rabin M,Cadwell C,Sampaio G,Cat I,Stratakis CA,Sandrini R

    更新日期:2001-07-31 00:00:00

  • Intensifying postfire weather and biological invasion drive species loss in a Mediterranean-type biodiversity hotspot.

    abstract::Prolonged periods of extreme heat or drought in the first year after fire affect the resilience and diversity of fire-dependent ecosystems by inhibiting seed germination or increasing mortality of seedlings and resprouting individuals. This interaction between weather and fire is of growing concern as climate changes,...

    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.1619014114

    authors: Slingsby JA,Merow C,Aiello-Lammens M,Allsopp N,Hall S,Kilroy Mollmann H,Turner R,Wilson AM,Silander JA Jr

    更新日期:2017-05-02 00:00:00

  • Effects of cerebral ischemia in mice deficient in Persephin.

    abstract::Persephin (Pspn), a recently cloned member of the transforming growth factor-beta superfamily (TGF-beta) and glial cell line-derived neurotrophic factor (GDNF) subfamily, is distributed throughout the nervous system at extremely low levels and is thought to function as a survival factor for midbrain dopaminergic and s...

    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.152535899

    authors: Tomac AC,Agulnick AD,Haughey N,Chang CF,Zhang Y,Bäckman C,Morales M,Mattson MP,Wang Y,Westphal H,Hoffer BJ

    更新日期:2002-07-09 00:00:00

  • Locking in alternate conformations of the integrin alphaLbeta2 I domain with disulfide bonds reveals functional relationships among integrin domains.

    abstract::We used integrin alphaLbeta2 heterodimers containing I domains locked open (active) or closed (inactive) with disulfide bonds to investigate regulatory interactions among domains in integrins. mAbs to the alphaL I domain and beta2 I-like domain inhibit adhesion of wild-type alphaLbeta2 to intercellular adhesion molecu...

    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.041618598

    authors: Lu C,Shimaoka M,Zang Q,Takagi J,Springer TA

    更新日期:2001-02-27 00:00:00

  • Pex1, a pollen-specific gene with an extensin-like domain.

    abstract::We report here the identification of a pollen-specific gene from Zea mays that contains multiple Ser-(Pro)n repeats, the motif found in the cell wall-associated extensins. Sequence analysis reveals that the encoded protein has a putative globular domain at the N terminus and an extensin-like domain at the C terminus. ...

    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.92.8.3086

    authors: Rubinstein AL,Broadwater AH,Lowrey KB,Bedinger PA

    更新日期:1995-04-11 00:00:00

  • Activation of the renal Na+:Cl- cotransporter by angiotensin II is a WNK4-dependent process.

    abstract::Pseudohypoaldosteronism type II is a salt-sensitive form of hypertension with hyperkalemia in humans caused by mutations in the with-no-lysine kinase 4 (WNK4). Several studies have shown that WNK4 modulates the activity of the renal Na(+)Cl(-) cotransporter, NCC. Because the renal consequences of WNK4 carrying pseudoa...

    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.1200947109

    authors: Castañeda-Bueno M,Cervantes-Pérez LG,Vázquez N,Uribe N,Kantesaria S,Morla L,Bobadilla NA,Doucet A,Alessi DR,Gamba G

    更新日期:2012-05-15 00:00:00

  • Stepwise assembly of the Nova-regulated alternative splicing network in the vertebrate brain.

    abstract::Novel organismal structures in metazoans are often undergirded by complex gene regulatory networks; as such, understanding the emergence of new structures through evolution requires reconstructing the series of evolutionary steps leading to these underlying networks. Here, we reconstruct the step-by-step assembly of t...

    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.1012333108

    authors: Irimia M,Denuc A,Burguera D,Somorjai I,Martín-Durán JM,Genikhovich G,Jimenez-Delgado S,Technau U,Roy SW,Marfany G,Garcia-Fernàndez J

    更新日期:2011-03-29 00:00:00

  • Intermolecular associations determine the dynamics of the circadian KaiABC oscillator.

    abstract::Three proteins from cyanobacteria (KaiA, KaiB, and KaiC) can reconstitute circadian oscillations in vitro. At least three molecular properties oscillate during this reaction, namely rhythmic phosphorylation of KaiC, ATP hydrolytic activity of KaiC, and assembly/disassembly of intermolecular complexes among KaiA, KaiB,...

    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.1002119107

    authors: Qin X,Byrne M,Mori T,Zou P,Williams DR,McHaourab H,Johnson CH

    更新日期:2010-08-17 00:00:00

  • The coactivator host cell factor-1 mediates Set1 and MLL1 H3K4 trimethylation at herpesvirus immediate early promoters for initiation of infection.

    abstract::Originally identified as an essential component of the herpes simplex virus immediate early (IE) gene enhancer complex, the transcriptional coactivator host cell factor-1 (HCF-1) has been implicated in a broad range of cellular regulatory circuits. The protein mediates activation through multiple interactions with tra...

    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.0704351104

    authors: Narayanan A,Ruyechan WT,Kristie TM

    更新日期:2007-06-26 00:00:00

  • Left-handed Z-DNA and in vivo supercoil density in the Escherichia coli chromosome.

    abstract::A system for studying Z-DNA formation in the Escherichia coli chromosome was developed. Prior investigations in recombinant plasmids showed that alternating (Pur-Pyr) sequences can adopt a left-handed Z-DNA conformation both in vitro and in vivo. We constructed mobile, transposon-based cassettes carrying cloned (Pur-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.91.21.9980

    authors: Lukomski S,Wells RD

    更新日期:1994-10-11 00:00:00

  • Limits to gene flow in a cosmopolitan marine planktonic diatom.

    abstract::The role of geographic isolation in marine microbial speciation is hotly debated because of the high dispersal potential and large population sizes of planktonic microorganisms and the apparent lack of strong dispersal barriers in the open sea. Here, we show that gene flow between distant populations of the globally d...

    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.1001380107

    authors: Casteleyn G,Leliaert F,Backeljau T,Debeer AE,Kotaki Y,Rhodes L,Lundholm N,Sabbe K,Vyverman W

    更新日期:2010-07-20 00:00:00

  • Bile acid stimulates hepatocyte polarization through a cAMP-Epac-MEK-LKB1-AMPK pathway.

    abstract::This study describes a unique function of taurocholate in bile canalicular formation involving signaling through a cAMP-Epac-MEK-Rap1-LKB1-AMPK pathway. In rat hepatocyte sandwich cultures, polarization was manifested by sequential progression of bile canaliculi from small structures to a fully branched network. Tauro...

    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.1018376108

    authors: Fu D,Wakabayashi Y,Lippincott-Schwartz J,Arias IM

    更新日期:2011-01-25 00:00:00

  • Site specific recA--independent recombination between bacterial plasmids: involvement of palindromes at the recombinational loci.

    abstract::A recA-independent recombinational event is described which results in insertion of an entire plasmid genome at a unique site of another plasmid, and coincident excision of a precisely defined DNA segment originally present at the point of the insertion. The resulting recombinant molecules subsequently can undergo sit...

    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.72.4.1373

    authors: Kopecko DJ,Cohen SN

    更新日期:1975-04-01 00:00:00

  • Two RNA polymerase complexes from vesicular stomatitis virus-infected cells that carry out transcription and replication of genome RNA.

    abstract::By immunoaffinity column chromatography, we have purified two RNA polymerase complexes, the transcriptase and replicase, from vesicular stomatitis virus-infected baby hamster kidney cells. The transcriptase is a multiprotein complex, containing the virus-encoded RNA polymerase L and P proteins, and two cellular protei...

    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.0401449101

    authors: Qanungo KR,Shaji D,Mathur M,Banerjee AK

    更新日期:2004-04-20 00:00:00

  • Multiple health and environmental impacts of foods.

    abstract::Food choices are shifting globally in ways that are negatively affecting both human health and the environment. Here we consider how consuming an additional serving per day of each of 15 foods is associated with 5 health outcomes in adults and 5 aspects of agriculturally driven environmental degradation. We find that ...

    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.1906908116

    authors: Clark MA,Springmann M,Hill J,Tilman D

    更新日期:2019-11-12 00:00:00

  • Fermentation of dihydroxyacetone by engineered Escherichia coli and Klebsiella variicola to products.

    abstract::Methane can be converted to triose dihydroxyacetone (DHA) by chemical processes with formaldehyde as an intermediate. Carbon dioxide, a by-product of various industries including ethanol/butanol biorefineries, can also be converted to formaldehyde and then to DHA. DHA, upon entry into a cell and phosphorylation to DHA...

    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.1801002115

    authors: Wang L,Chauliac D,Rhee MS,Panneerselvam A,Ingram LO,Shanmugam KT

    更新日期:2018-04-24 00:00:00

  • Ca2+-dependent and -independent interactions of the isoforms of the alpha1A subunit of brain Ca2+ channels with presynaptic SNARE proteins.

    abstract::Fast neurotransmission requires that docked synaptic vesicles be located near the presynaptic N-type or P/Q-type calcium channels. Specific protein-protein interactions between a synaptic protein interaction (synprint) site on N-type and P/Q-type channels and the presynaptic SNARE proteins syntaxin, SNAP-25, and synap...

    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.94.26.14782

    authors: Kim DK,Catterall WA

    更新日期:1997-12-23 00:00:00

  • Engineering of protease variants exhibiting high catalytic activity and exquisite substrate selectivity.

    abstract::The exquisite selectivity and catalytic activity of enzymes have been shaped by the effects of positive and negative selection pressure during the course of evolution. In contrast, enzyme variants engineered by using in vitro screening techniques to accept novel substrates typically display a higher degree of catalyti...

    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.0500063102

    authors: Varadarajan N,Gam J,Olsen MJ,Georgiou G,Iverson BL

    更新日期:2005-05-10 00:00:00

  • A role for heme in Alzheimer's disease: heme binds amyloid beta and has altered metabolism.

    abstract::Heme is a common factor linking several metabolic perturbations in Alzheimer's disease (AD), including iron metabolism, mitochondrial complex IV, heme oxygenase, and bilirubin. Therefore, we determined whether heme metabolism was altered in temporal lobes obtained at autopsy from AD patients and age-matched nondemente...

    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.0404349101

    authors: Atamna H,Frey WH 2nd

    更新日期:2004-07-27 00:00:00

  • Cross-linking reveals laminin coiled-coil architecture.

    abstract::Laminin, an ∼800-kDa heterotrimeric protein, is a major functional component of the extracellular matrix, contributing to tissue development and maintenance. The unique architecture of laminin is not currently amenable to determination at high resolution, as its flexible and narrow segments complicate both crystalliza...

    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.1608424113

    authors: Armony G,Jacob E,Moran T,Levin Y,Mehlman T,Levy Y,Fass D

    更新日期:2016-11-22 00:00:00

  • Effect of glycosylation on protein folding: a close look at thermodynamic stabilization.

    abstract::Glycosylation is one of the most common posttranslational modifications to occur in protein biosynthesis, yet its effect on the thermodynamics and kinetics of proteins is poorly understood. A minimalist model based on the native protein topology, in which each amino acid and sugar ring was represented by a single bead...

    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.0801340105

    authors: Shental-Bechor D,Levy Y

    更新日期:2008-06-17 00:00:00

  • Role for Bcl-xL as an inhibitor of cytosolic cytochrome C accumulation in DNA damage-induced apoptosis.

    abstract::Cytochrome C is a mitochondrial protein that induces apoptosis when released into the cytosol or when added to cell-free extracts. Here we show that cells that overexpress the Bcl-2-related protein Bcl-xL fail to accumulate cytosolic cytochrome C or undergo apoptosis in response to genotoxic stress. Coimmunoprecipitat...

    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.94.13.6939

    authors: Kharbanda S,Pandey P,Schofield L,Israels S,Roncinske R,Yoshida K,Bharti A,Yuan ZM,Saxena S,Weichselbaum R,Nalin C,Kufe D

    更新日期:1997-06-24 00:00:00

  • Specific monosaccharide inhibition of active sodium channels in neuroblastoma cells.

    abstract::L-Fucose and D-galactose in low concentrations (0.27 or 2.7 mM) inhibited the induction of active Na+ channels in mouse and human neuroblastoma cells when the monosaccharides were added to the culture medium for 4 days with the inducing agent dimethyl sulfoxide. Active Na+ ionophores were determined by measurement 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.78.2.1250

    authors: Giovanni MY,Kessel D,Glick MC

    更新日期:1981-02-01 00:00:00

  • Mode of action and resistance studies unveil new roles for tropodithietic acid as an anticancer agent and the γ-glutamyl cycle as a proton sink.

    abstract::While we have come to appreciate the architectural complexity of microbially synthesized secondary metabolites, far less attention has been paid to linking their structural features with possible modes of action. This is certainly the case with tropodithietic acid (TDA), a broad-spectrum antibiotic generated by marine...

    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.1518034113

    authors: Wilson MZ,Wang R,Gitai Z,Seyedsayamdost MR

    更新日期:2016-02-09 00:00:00

  • Molecular cloning and expression of an additional epidermal growth factor receptor-related gene.

    abstract::Epidermal growth factor (EGF), transforming growth factor alpha (TGF-alpha), and amphiregulin are structurally and functionally related growth regulatory proteins. These secreted polypeptides all bind to the 170-kDa cell-surface EGF receptor, activating its intrinsic kinase activity. However, amphiregulin exhibits dif...

    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.87.13.4905

    authors: Plowman GD,Whitney GS,Neubauer MG,Green JM,McDonald VL,Todaro GJ,Shoyab M

    更新日期:1990-07-01 00:00:00

  • Anacardic acid induces IL-33 and promotes remyelination in CNS.

    abstract::Given the known neuroreparative actions of IL-33 in experimental models of central nervous system (CNS) injury, we predicted that compounds which induce IL-33 are likely to promote remyelination. We found anacardic acid as a candidate molecule to serve as a therapeutic agent to promote remyelination. Addition of anaca...

    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.2006566117

    authors: Ljunggren-Rose Å,Natarajan C,Matta P,Pandey A,Upender I,Sriram S

    更新日期:2020-09-01 00:00:00

  • The law of perceptual stability: well-definedness and validity.

    abstract::Axiomatic foundations for a theory of perception have been given in a prior communication [Shiman, L. G. (1978) Proc. Natl. Acad. Sci. USA 75, 2049-2053]. The theory is based on mathematically characterized stable images. Stable images model subjective (psychological) states of observers. We showed there is a universa...

    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.75.5.2535

    authors: Shiman LG

    更新日期:1978-05-01 00:00:00