Utilization of extracellular information before ligand-receptor binding reaches equilibrium expands and shifts the input dynamic range.

Abstract:

:Cell signaling systems sense and respond to ligands that bind cell surface receptors. These systems often respond to changes in the concentration of extracellular ligand more rapidly than the ligand equilibrates with its receptor. We demonstrate, by modeling and experiment, a general "systems level" mechanism cells use to take advantage of the information present in the early signal, before receptor binding reaches a new steady state. This mechanism, pre-equilibrium sensing and signaling (PRESS), operates in signaling systems in which the kinetics of ligand-receptor binding are slower than the downstream signaling steps, and it typically involves transient activation of a downstream step. In the systems where it operates, PRESS expands and shifts the input dynamic range, allowing cells to make different responses to ligand concentrations so high as to be otherwise indistinguishable. Specifically, we show that PRESS applies to the yeast directional polarization in response to pheromone gradients. Consideration of preexisting kinetic data for ligand-receptor interactions suggests that PRESS operates in many cell signaling systems throughout biology. The same mechanism may also operate at other levels in signaling systems in which a slow activation step couples to a faster downstream step.

authors

Ventura AC,Bush A,Vasen G,Goldín MA,Burkinshaw B,Bhattacharjee N,Folch A,Brent R,Chernomoretz A,Colman-Lerner A

doi

10.1073/pnas.1322761111

subject

Has Abstract

pub_date

2014-09-16 00:00:00

pages

E3860-9

issue

37

eissn

0027-8424

issn

1091-6490

pii

1322761111

journal_volume

111

pub_type

杂志文章
  • Comparison of the NMR solution structure and the x-ray crystal structure of rat metallothionein-2.

    abstract::Metallothioneins are small cysteine-rich proteins capable of binding heavy metal ions such as Zn2+ and Cd2+. They are ubiquitous tissue components in higher organisms, which tentatively have been attributed both unspecific protective functions against toxic metal ions and highly specific roles in fundamental zinc-regu...

    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.89.21.10124

    authors: Braun W,Vasák M,Robbins AH,Stout CD,Wagner G,Kägi JH,Wüthrich K

    更新日期:1992-11-01 00:00:00

  • Mathematical approaches to comparative linguistics.

    abstract::The inference of the evolutionary history of a set of languages is a complex problem. Although some languages are known to be related through descent from common ancestral languages, for other languages determining whether such a relationship holds is itself a difficult problem. In this paper we report on new methods,...

    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.94.13.6585

    authors: Warnow T

    更新日期:1997-06-24 00:00:00

  • Increased cell proliferation and neurogenesis in the adult human Huntington's disease brain.

    abstract::Neurogenesis has recently been observed in the adult human brain, suggesting the possibility of endogenous neural repair. However, the augmentation of neurogenesis in the adult human brain in response to neuronal cell loss has not been demonstrated. This study was undertaken to investigate whether neurogenesis occurs ...

    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.1532244100

    authors: Curtis MA,Penney EB,Pearson AG,van Roon-Mom WM,Butterworth NJ,Dragunow M,Connor B,Faull RL

    更新日期:2003-07-22 00:00:00

  • Stimulation of simian virus 40 late gene expression by simian virus 40 tumor antigen.

    abstract::The early simian virus 40 (SV40) gene product, large tumor (T) antigen, is responsible for the initiation of viral DNA replication and the autoregulation of early gene expression through direct protein-DNA interactions. We investigated the role of T antigen in late viral gene expression, independent of its function in...

    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.81.7.2040

    authors: Brady J,Bolen JB,Radonovich M,Salzman N,Khoury G

    更新日期:1984-04-01 00:00:00

  • A biosensor assay for studying ligand-membrane receptor interactions: binding of antibodies and HIV-1 Env to chemokine receptors.

    abstract::The HIV envelope (Env) protein mediates entry into cells by binding CD4 and an appropriate coreceptor, which triggers structural changes in Env that lead to fusion between the viral and cellular membranes. The major HIV-1 coreceptors are the seven transmembrane domain chemokine receptors CCR5 and CXCR4. The type of co...

    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.190274097

    authors: Hoffman TL,Canziani G,Jia L,Rucker J,Doms RW

    更新日期:2000-10-10 00:00:00

  • Formation of an RNA primer for initiation of replication of ColE1 DNA by ribonuclease H.

    abstract::A plasmid that consists of an 812-base-pair segment containing the replication origin of plasmid ColE1 and of a 1240-base-pair segment containing a beta-lactamase gene has been constructed. The plasmid DNA has three principal sites where transcription is initiated in vitro. One is located in the ColE1 segment 555 nucl...

    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.77.5.2450

    authors: Itoh T,Tomizawa J

    更新日期:1980-05-01 00:00:00

  • Parental divorce is not uniformly disruptive to children's educational attainment.

    abstract::Children whose parents divorce tend to have worse educational outcomes than children whose parents stay married. However, not all children respond identically to their parents divorcing. We focus on how the impact of parental divorce on children's education varies by how likely or unlikely divorce was for those parent...

    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.1813049116

    authors: Brand JE,Moore R,Song X,Xie Y

    更新日期:2019-04-09 00:00:00

  • Declining survival probability threatens the North Atlantic right whale.

    abstract::The North Atlantic northern right whale (Eubalaena glacialis) is considered the most endangered large whale species. Its population has recovered only slowly since the cessation of commercial whaling and numbers about 300 individuals. We applied mark-recapture statistics to a catalog of photographically identified ind...

    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.96.6.3308

    authors: Caswell H,Fujiwara M,Brault S

    更新日期:1999-03-16 00:00:00

  • Dendritic field size and morphology of midget and parasol ganglion cells of the human retina.

    abstract::The visual system of the macaque monkey has provided a useful model for understanding the neural basis of human vision, yet, there are few detailed comparisons of neural populations other than photoreceptors for the two species. Using intracellular staining in an in vitro preparation of the isolated and intact human r...

    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.89.20.9666

    authors: Dacey DM,Petersen MR

    更新日期:1992-10-15 00:00:00

  • Metabolic heterogeneity in human calf muscle during maximal exercise.

    abstract::Human skeletal muscle is composed of various muscle fiber types. We hypothesized that differences in metabolism between fiber types could be detected noninvasively with 31P nuclear magnetic resonance spectroscopy during maximal exercise. This assumes that during maximal exercise all fiber types are recruited and all v...

    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.88.13.5714

    authors: Vandenborne K,McCully K,Kakihira H,Prammer M,Bolinger L,Detre JA,De Meirlier K,Walter G,Chance B,Leigh JS

    更新日期:1991-07-01 00:00:00

  • Radiocarbon dates and Bayesian modeling support maritime diffusion model for megaliths in Europe.

    abstract::There are two competing hypotheses for the origin of megaliths in Europe. The conventional view from the late 19th and early 20th centuries was of a single-source diffusion of megaliths in Europe from the Near East through the Mediterranean and along the Atlantic coast. Following early radiocarbon dating in the 1970s,...

    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.1813268116

    authors: Schulz Paulsson B

    更新日期:2019-02-26 00:00:00

  • Surface attachment induces Pseudomonas aeruginosa virulence.

    abstract::Pseudomonas aeruginosa infects every type of host that has been examined by deploying multiple virulence factors. Previous studies of virulence regulation have largely focused on chemical cues, but P. aeruginosa may also respond to mechanical cues. Using a rapid imaging-based virulence assay, we demonstrate that P. ae...

    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.1415712111

    authors: Siryaporn A,Kuchma SL,O'Toole GA,Gitai Z

    更新日期:2014-11-25 00:00:00

  • Direct observation of hydrogen atom dynamics and interactions by ultrahigh resolution neutron protein crystallography.

    abstract::The 1.1 Å, ultrahigh resolution neutron structure of hydrogen/deuterium (H/D) exchanged crambin is reported. Two hundred ninety-nine out of 315, or 94.9%, of the hydrogen atom positions in the protein have been experimentally derived and resolved through nuclear density maps. A number of unconventional interactions ar...

    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.1208341109

    authors: Chen JC,Hanson BL,Fisher SZ,Langan P,Kovalevsky AY

    更新日期:2012-09-18 00:00:00

  • Dynamic phase transitions in freestanding polymer thin films.

    abstract::After more than two decades of study, many fundamental questions remain unanswered about the dynamics of glass-forming materials confined to thin films. Experiments and simulations indicate that free interfaces enhance dynamics over length scales larger than molecular sizes, and this effect strengthens at lower temper...

    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.2006703117

    authors: Ivancic RJS,Riggleman RA

    更新日期:2020-10-13 00:00:00

  • Counting the number of releasable synaptic vesicles in a presynaptic terminal.

    abstract::Synaptic transmission depends on the continued availability of neurotransmitter-filled synaptic vesicles (SVs) for triggered release from presynaptic boutons. Surprisingly, small boutons in the brain, that already contain comparatively few SVs, are thought to retain the majority of these SVs in a "reserve" pool that i...

    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.0811017106

    authors: Ikeda K,Bekkers JM

    更新日期:2009-02-24 00:00:00

  • Dynamics of enzymatic reactions.

    abstract::The detailed molecular dynamics of an actual bond-breaking event in a fluctuating enzyme substrate complex is simulated. The method developed allows one to explore what type of fluctuations are involved in enzymatic reactions and to evaluate entropic contributions to enzyme catalysis. The fluctuations of the enzyme el...

    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.81.2.444

    authors: Warshel A

    更新日期:1984-01-01 00:00:00

  • Major diversification of voltage-gated K+ channels occurred in ancestral parahoxozoans.

    abstract::We examined the origins and functional evolution of the Shaker and KCNQ families of voltage-gated K(+) channels to better understand how neuronal excitability evolved. In bilaterians, the Shaker family consists of four functionally distinct gene families (Shaker, Shab, Shal, and Shaw) that share a subunit structure co...

    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.1422941112

    authors: Li X,Liu H,Chu Luo J,Rhodes SA,Trigg LM,van Rossum DB,Anishkin A,Diatta FH,Sassic JK,Simmons DK,Kamel B,Medina M,Martindale MQ,Jegla T

    更新日期:2015-03-03 00:00:00

  • Anomalous anisotropic compression behavior of superconducting CrAs under high pressure.

    abstract::CrAs was observed to possess the bulk superconductivity under high-pressure conditions. To understand the superconducting mechanism and explore the correlation between the structure and superconductivity, the high-pressure structural evolution of CrAs was investigated using the angle-dispersive X-ray diffraction (XRD)...

    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.1520570112

    authors: Yu Z,Wu W,Hu Q,Zhao J,Li C,Yang K,Cheng J,Luo J,Wang L,Mao HK

    更新日期:2015-12-01 00:00:00

  • Free radical functionalization of surfaces to prevent adverse responses to biomedical devices.

    abstract::Immobilizing a protein, that is fully compatible with the patient, on the surface of a biomedical device should make it possible to avoid adverse responses such as inflammation, rejection, or excessive fibrosis. A surface that strongly binds and does not denature the compatible protein is required. Hydrophilic surface...

    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.1103277108

    authors: Bilek MM,Bax DV,Kondyurin A,Yin Y,Nosworthy NJ,Fisher K,Waterhouse A,Weiss AS,dos Remedios CG,McKenzie DR

    更新日期:2011-08-30 00:00:00

  • Netrin-1 induces angiogenesis via a DCC-dependent ERK1/2-eNOS feed-forward mechanism.

    abstract::Netrin-1 is critical for axonal pathfinding which shares similarities with formation of vascular network. Here we report that netrin-1 induction of angiogenesis is mediated by an increase in endothelial nitric oxide (NO*) production, which occurs via a DCC-dependent, ERK1/2-eNOS feed-forward mechanism. Exposure of mat...

    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.0511011103

    authors: Nguyen A,Cai H

    更新日期:2006-04-25 00:00:00

  • From the Cover: Antarctic climate signature in the Greenland ice core record.

    abstract::A numerical algorithm is applied to the Greenland Ice Sheet Project 2 (GISP2) dust record from Greenland to remove the abrupt changes in dust flux associated with the Dansgaard-Oeschger (D-O) oscillations of the last glacial period. The procedure is based on the assumption that the rapid changes in dust are associated...

    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.0708494104

    authors: Barker S,Knorr G

    更新日期:2007-10-30 00:00:00

  • Intraoperative mass spectrometry mapping of an onco-metabolite to guide brain tumor surgery.

    abstract::For many intraoperative decisions surgeons depend on frozen section pathology, a technique developed over 150 y ago. Technical innovations that permit rapid molecular characterization of tissue samples at the time of surgery are needed. Here, using desorption electrospray ionization (DESI) MS, we rapidly detect the tu...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 临床试验,杂志文章

    doi:10.1073/pnas.1404724111

    authors: Santagata S,Eberlin LS,Norton I,Calligaris D,Feldman DR,Ide JL,Liu X,Wiley JS,Vestal ML,Ramkissoon SH,Orringer DA,Gill KK,Dunn IF,Dias-Santagata D,Ligon KL,Jolesz FA,Golby AJ,Cooks RG,Agar NY

    更新日期:2014-07-29 00:00:00

  • Association of mitochondria with microtubules in cultured cells.

    abstract::By indirect immunofluorescence techniques, microtubules and mitochondria were localized in normal rat kidney cells, human WI38 fibroblasts, mouse peritoneal macrophages, and a putative smooth muscle rat cell line, in monolayer culture. The mitochondria were found to be arranged along the cytoplasmic microtubules in ea...

    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.75.8.3863

    authors: Heggeness MH,Simon M,Singer SJ

    更新日期:1978-08-01 00:00:00

  • Nuclear carbonic anhydrase 6B associates with PRMT5 to epigenetically promote IL-12 expression in innate response.

    abstract::Interleukin-12 (IL-12) is critical for induction of protective immunity against intracellular bacterial infection. However, the mechanisms for efficient induction of IL-12 in innate response remain poorly understood. Here we report that the B type of carbonic anhydrase 6 (Car6-b, which encoded CA-VI B) is essential fo...

    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.1700917114

    authors: Xu J,Xu X,Wang B,Ma Y,Zhang L,Xu H,Hu Y,Wu J,Cao X

    更新日期:2017-08-08 00:00:00

  • Simian virus 40 small tumor antigen and an amino-terminal domain of large tumor antigen share a common transforming function.

    abstract::The 82-residue amino-terminal sequences of simian virus 40 large tumor antigen (TAg) and small tumor antigen (tAg) are identical. Genetic analysis of TAg lacking amino acids 1-82 revealed that it was transformation-defective, as revealed by the agar growth assay, except when introduced in the presence of tAg. Since th...

    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.87.19.7448

    authors: Montano X,Millikan R,Milhaven JM,Newsom DA,Ludlow JW,Arthur AK,Fanning E,Bikel I,Livingston DM

    更新日期:1990-10-01 00:00:00

  • Activation of the p53 pathway by small-molecule-induced MDM2 and MDMX dimerization.

    abstract::Activation of p53 tumor suppressor by antagonizing its negative regulator murine double minute (MDM)2 has been considered an attractive strategy for cancer therapy and several classes of p53-MDM2 binding inhibitors have been developed. However, these compounds do not inhibit the p53-MDMX interaction, and their effecti...

    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.1203789109

    authors: Graves B,Thompson T,Xia M,Janson C,Lukacs C,Deo D,Di Lello P,Fry D,Garvie C,Huang KS,Gao L,Tovar C,Lovey A,Wanner J,Vassilev LT

    更新日期:2012-07-17 00:00:00

  • Ocular cicatricial pemphigoid antigen: partial sequence and biochemical characterization.

    abstract::Ocular cicatricial pemphigoid (OCP) is an autoimmune disease that affects mainly conjunctiva and other squamous epithelia. OCP is histologically characterized by a separation of the epithelium from underlying tissues within the basement membrane zone. Immunopathological studies demonstrate the deposition of anti-basem...

    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.93.25.14714

    authors: Tyagi S,Bhol K,Natarajan K,Livir-Rallatos C,Foster CS,Ahmed AR

    更新日期:1996-12-10 00:00:00

  • Reiterative AP2a activity controls sequential steps in the neural crest gene regulatory network.

    abstract::The neural crest (NC) emerges from combinatorial inductive events occurring within its progenitor domain, the neural border (NB). Several transcription factors act early at the NB, but the initiating molecular events remain elusive. Recent data from basal vertebrates suggest that ap2 might have been critical for NC em...

    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.1010740107

    authors: de Crozé N,Maczkowiak F,Monsoro-Burq AH

    更新日期:2011-01-04 00:00:00

  • Cyclin E, a redundant cyclin in breast cancer.

    abstract::Cyclin E is an important regulator of cell cycle progression that together with cyclin-dependent kinase (cdk) 2 is crucial for the G1/S transition during the mammalian cell cycle. Previously, we showed that severe overexpression of cyclin E protein in tumor cells and tissues results in the appearance of lower molecula...

    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.93.26.15215

    authors: Gray-Bablin J,Zalvide J,Fox MP,Knickerbocker CJ,DeCaprio JA,Keyomarsi K

    更新日期:1996-12-24 00:00:00

  • Phosphorylation-induced unfolding regulates p19INK4d during the human cell cycle.

    abstract::Cell cycle progression is tightly regulated by cyclin-dependent kinases (CDKs). The ankyrin-repeat protein p19INK4d functions as a key regulator of G1/S transition; however, its molecular mode of action is unknown. Here, we combine cell and structural biology methods to unravel the mechanism by which p19INK4d controls...

    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.1719774115

    authors: Kumar A,Gopalswamy M,Wolf A,Brockwell DJ,Hatzfeld M,Balbach J

    更新日期:2018-03-27 00:00:00