Biophysical mechanism of T-cell receptor triggering in a reconstituted system.

Abstract:

:A T-cell-mediated immune response is initiated by the T-cell receptor (TCR) interacting with peptide-bound major histocompatibility complex (pMHC) on an infected cell. The mechanism by which this interaction triggers intracellular phosphorylation of the TCR, which lacks a kinase domain, remains poorly understood. Here, we have introduced the TCR and associated signalling molecules into a non-immune cell and reconstituted ligand-specific signalling when these cells are conjugated with antigen-presenting cells. We show that signalling requires the differential segregation of a phosphatase and kinase in the plasma membrane. An artificial, chemically controlled receptor system generates the same effect as TCR–pMHC, demonstrating that the binding energy of an extracellular protein–protein interaction can drive the spatial segregation of membrane proteins without a transmembrane conformational change. This general mechanism may extend to other receptors that rely on extrinsic kinases, including, as we demonstrate, chimaeric antigen receptors being developed for cancer immunotherapy.

journal_name

Nature

journal_title

Nature

authors

James JR,Vale RD

doi

10.1038/nature11220

subject

Has Abstract

pub_date

2012-07-05 00:00:00

pages

64-9

issue

7405

eissn

0028-0836

issn

1476-4687

pii

nature11220

journal_volume

487

pub_type

杂志文章

相关文献

NATURE文献大全
  • Possible role for salivary gland protein in taste reception indicated by homology to lipophilic-ligand carrier proteins.

    abstract::Sensory transduction in taste and olfaction, the principal chemical senses, seems to be mediated by membrane-associated proteins on the apical surfaces of the respective receptor cells. The recent isolation and characterization of soluble 'odorant-binding proteins' secreted from the nasal glands of rat, cow and frog, ...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/343366a0

    authors: Schmale H,Holtgreve-Grez H,Christiansen H

    更新日期:1990-01-25 00:00:00

  • Structural analysis of murine genes containing homoeo box sequences and their expression in embryonal carcinoma cells.

    abstract::The presence of homoeo box sequences in the genomes of vertebrates has suggested that these metazoans possess the equivalent of the homoeotic genes that have a key role in regulating the development of the fruitfly Drosophila melanogaster. We report here that a novel murine homoeo box-containing gene is expressed in e...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/314713a0

    authors: Colberg-Poley AM,Voss SD,Chowdhury K,Gruss P

    更新日期:1985-04-25 00:00:00

  • A negatively powered lens in the chameleon.

    abstract::Chameleons are arboral lizards that spot their prey visually and catch it by highly precise shots with their long sticky tongue. They scan their environment by large-amplitude independent saccadic eye movements; once an insect is detected, the head axis is aligned towards the target ('head tracking', both eyes come fo...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/373692a0

    authors: Ott M,Schaeffel F

    更新日期:1995-02-23 00:00:00

  • Articulated Palaeozoic fossil with 17 plates greatly expands disparity of early chitons.

    abstract::Modern chitons (Mollusca: Polyplacophora) possess a highly conserved skeleton of eight shell plates (valves) surrounded by spicules or scales, and fossil evidence suggests that the chiton skeleton has changed little since the first appearance of the class in the Late Cambrian period (about 500 million years before pre...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/nature02548

    authors: Vendrasco MJ,Wood TE,Runnegar BN

    更新日期:2004-05-20 00:00:00

  • A massive star origin for an unusual helium-rich supernova in an elliptical galaxy.

    abstract::The unusual helium-rich (type Ib) supernova SN 2005E is distinguished from all supernovae hitherto observed by its faint and rapidly fading light curve, prominent calcium lines in late-phase spectra and lack of any mark of recent star formation near the supernova location. These properties are claimed to be explained ...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/nature09055

    authors: Kawabata KS,Maeda K,Nomoto K,Taubenberger S,Tanaka M,Deng J,Pian E,Hattori T,Itagaki K

    更新日期:2010-05-20 00:00:00

  • Eomesodermin is required for mouse trophoblast development and mesoderm formation.

    abstract::The earliest cell fate decision in the mammalian embryo separates the extra-embryonic trophoblast lineage, which forms the fetal portion of the placenta, from the embryonic cell lineages. The body plan of the embryo proper is established only later at gastrulation, when the pluripotent epiblast gives rise to the germ ...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/35003601

    authors: Russ AP,Wattler S,Colledge WH,Aparicio SA,Carlton MB,Pearce JJ,Barton SC,Surani MA,Ryan K,Nehls MC,Wilson V,Evans MJ

    更新日期:2000-03-02 00:00:00

  • Nucleation of microtubule assembly by a gamma-tubulin-containing ring complex.

    abstract::The highly conserved protein gamma-tubulin is required for microtubule nucleation in vivo. When viewed in the electron microscope, a highly purified gamma-tubulin complex from Xenopus consisting of at least seven different proteins is seen to have an open ring structure. This complex acts as an active microtubule-nucl...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/378578a0

    authors: Zheng Y,Wong ML,Alberts B,Mitchison T

    更新日期:1995-12-07 00:00:00

  • cAMP signalling in mushroom bodies modulates temperature preference behaviour in Drosophila.

    abstract::Homoiotherms, for example mammals, regulate their body temperature with physiological responses such as a change of metabolic rate and sweating. In contrast, the body temperature of poikilotherms, for example Drosophila, is the result of heat exchange with the surrounding environment as a result of the large ratio of ...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/nature07090

    authors: Hong ST,Bang S,Hyun S,Kang J,Jeong K,Paik D,Chung J,Kim J

    更新日期:2008-08-07 00:00:00

  • Perspectives for vascular genomics.

    abstract::Diseases of the vascular system result from a complex mixture of genetic and environmental factors. Data sets, technologies and strategies emanating from the human genome programme have been applied to the analysis of both rare single-gene and common multigenic vascular disorders. Genomic approaches including inter- a...

    journal_title:Nature

    pub_type: 杂志文章,评审

    doi:10.1038/35025236

    authors: Rubin EM,Tall A

    更新日期:2000-09-14 00:00:00

  • Supernova SN 2011fe from an exploding carbon-oxygen white dwarf star.

    abstract::Type Ia supernovae have been used empirically as 'standard candles' to demonstrate the acceleration of the expansion of the Universe even though fundamental details, such as the nature of their progenitor systems and how the stars explode, remain a mystery. There is consensus that a white dwarf star explodes after acc...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/nature10644

    authors: Nugent PE,Sullivan M,Cenko SB,Thomas RC,Kasen D,Howell DA,Bersier D,Bloom JS,Kulkarni SR,Kandrashoff MT,Filippenko AV,Silverman JM,Marcy GW,Howard AW,Isaacson HT,Maguire K,Suzuki N,Tarlton JE,Pan YC,Bildsten L,Ful

    更新日期:2011-12-14 00:00:00

  • Preferential expression of the T-cell receptor V beta 3 gene by Mlsc reactive T cells.

    abstract::The precursor frequency of T cells specific for any given foreign antigen is, in general, extremely low. Prominent exceptions to this rule are the T cells that are specific for foreign major histocompatibility complex (MHC) products or for products of the minor lymphocyte stimulatory (Mls) genes in the mouse which are...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/335827a0

    authors: Abe R,Vacchio MS,Fox B,Hodes RJ

    更新日期:1988-10-27 00:00:00

  • A salmonella protein antagonizes Rac-1 and Cdc42 to mediate host-cell recovery after bacterial invasion.

    abstract::An essential feature of the bacterial pathogen Salmonella spp. is its ability to enter cells that are normally non-phagocytic, such as those of the intestinal epithelium. The bacterium achieves entry by delivering effector proteins into the host-cell cytosol by means of a specialized protein-secretion system (termed t...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/45829

    authors: Fu Y,Galán JE

    更新日期:1999-09-16 00:00:00

  • Osteoprotection by semaphorin 3A.

    abstract::The bony skeleton is maintained by local factors that regulate bone-forming osteoblasts and bone-resorbing osteoclasts, in addition to hormonal activity. Osteoprotegerin protects bone by inhibiting osteoclastic bone resorption, but no factor has yet been identified as a local determinant of bone mass that regulates bo...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/nature11000

    authors: Hayashi M,Nakashima T,Taniguchi M,Kodama T,Kumanogoh A,Takayanagi H

    更新日期:2012-05-03 00:00:00

  • Plate tectonics, damage and inheritance.

    abstract::The initiation of plate tectonics on Earth is a critical event in our planet's history. The time lag between the first proto-subduction (about 4 billion years ago) and global tectonics (approximately 3 billion years ago) suggests that plates and plate boundaries became widespread over a period of 1 billion years. The ...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/nature13072

    authors: Bercovici D,Ricard Y

    更新日期:2014-04-24 00:00:00

  • Activation of stress-activated protein kinase by MEKK1 phosphorylation of its activator SEK1.

    abstract::A kinase distinct from the MEK activator Raf, termed MEK kinase-1 (MEKK), was originally identified by virtue of its homology to kinases involved in yeast mating signal cascades. Like Raf, MEKK is capable of activating MEK in vitro. High-level expression of MEKK in COS-7 cells or using vaccinia virus vectors also acti...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/372798a0

    authors: Yan M,Dai T,Deak JC,Kyriakis JM,Zon LI,Woodgett JR,Templeton DJ

    更新日期:1994-12-22 00:00:00

  • Muscle force is generated by myosin heads stereospecifically attached to actin.

    abstract::Muscle force is generated by myosin crossbridges interacting with actin. As estimated from stiffness and equatorial X-ray diffraction of muscle and muscle fibres, most myosin crossbridges are attached to actin during isometric contraction, but a much smaller fraction is bound stereospecifically. To determine the fract...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/40651

    authors: Bershitsky SY,Tsaturyan AK,Bershitskaya ON,Mashanov GI,Brown P,Burns R,Ferenczi MA

    更新日期:1997-07-10 00:00:00

  • Demonstration by genetic suppression of interaction of GroE products with many proteins.

    abstract::The way in which proteins attain and maintain their final form is of fundamental importance. Recent work has focused on the role of a set of ubiquitous proteins, termed chaperonins, in the assembly of phage and multisubunit proteins. The range of chaperonin action is unknown; they could interact with most cellular pol...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/342451a0

    authors: Van Dyk TK,Gatenby AA,LaRossa RA

    更新日期:1989-11-23 00:00:00

  • Cryo-EM structure of human rhodopsin bound to an inhibitory G protein.

    abstract::G-protein-coupled receptors comprise the largest family of mammalian transmembrane receptors. They mediate numerous cellular pathways by coupling with downstream signalling transducers, including the hetrotrimeric G proteins Gs (stimulatory) and Gi (inhibitory) and several arrestin proteins. The structural mechanisms ...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/s41586-018-0215-y

    authors: Kang Y,Kuybeda O,de Waal PW,Mukherjee S,Van Eps N,Dutka P,Zhou XE,Bartesaghi A,Erramilli S,Morizumi T,Gu X,Yin Y,Liu P,Jiang Y,Meng X,Zhao G,Melcher K,Ernst OP,Kossiakoff AA,Subramaniam S,Xu HE

    更新日期:2018-06-01 00:00:00

  • Evidence for only minor contributions from bacteria to sedimentary organic carbon.

    abstract::Because their molecular signatures are often prominent in extracts of sediments, bacteria are thought to be important contributors to petroleum source beds. It has been shown recently, however, that abundances of biomarkers do not always reflect relative contributions to sedimentary organic carbon (Corg). The contrib...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/369224a0

    authors: Hartgers WA,Sinninghe Damste JS,Requejo AG,Allan J,Hayes JM,de Leeuw JW

    更新日期:1994-05-19 00:00:00

  • Effect of age on benzodiazepine-induced behavioural convulsions in rats.

    abstract::The benzodiazepines are a class of drugs used to alleviate anxiety. As such they constitute one of the most commonly prescribed compounds, due in part to their efficacy and safety. The physiological effect of these drugs is probably through interactions with a low affinity benzodiazepine binding site and two (types 1 ...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/302431a0

    authors: Barr GA,Lithgow T

    更新日期:1983-03-31 00:00:00

  • Ab initio alpha-alpha scattering.

    abstract::Processes such as the scattering of alpha particles ((4)He), the triple-alpha reaction, and alpha capture play a major role in stellar nucleosynthesis. In particular, alpha capture on carbon determines the ratio of carbon to oxygen during helium burning, and affects subsequent carbon, neon, oxygen, and silicon burning...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/nature16067

    authors: Elhatisari S,Lee D,Rupak G,Epelbaum E,Krebs H,Lähde TA,Luu T,Meißner UG

    更新日期:2015-12-03 00:00:00

  • Extreme oxygen isotope ratios in the early Solar System.

    abstract::The origins of the building blocks of the Solar System can be studied using the isotopic composition of early planetary and meteoritic material. Oxygen isotopes in planetary materials show variations at the per cent level that are not related to the mass of the isotopes; rather, they result from the mixture of compone...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/nature03947

    authors: Aléon J,Robert F,Duprat J,Derenne S

    更新日期:2005-09-15 00:00:00

  • MC4R-dependent suppression of appetite by bone-derived lipocalin 2.

    abstract::Bone has recently emerged as a pleiotropic endocrine organ that secretes at least two hormones, FGF23 and osteocalcin, which regulate kidney function and glucose homeostasis, respectively. These findings have raised the question of whether other bone-derived hormones exist and what their potential functions are. Here ...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/nature21697

    authors: Mosialou I,Shikhel S,Liu JM,Maurizi A,Luo N,He Z,Huang Y,Zong H,Friedman RA,Barasch J,Lanzano P,Deng L,Leibel RL,Rubin M,Nickolas T,Chung W,Zeltser LM,Williams KW,Pessin JE,Kousteni S

    更新日期:2017-03-16 00:00:00

  • Targeting C-reactive protein for the treatment of cardiovascular disease.

    abstract::Complement-mediated inflammation exacerbates the tissue injury of ischaemic necrosis in heart attacks and strokes, the most common causes of death in developed countries. Large infarct size increases immediate morbidity and mortality and, in survivors of the acute event, larger non-functional scars adversely affect lo...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/nature04672

    authors: Pepys MB,Hirschfield GM,Tennent GA,Gallimore JR,Kahan MC,Bellotti V,Hawkins PN,Myers RM,Smith MD,Polara A,Cobb AJ,Ley SV,Aquilina JA,Robinson CV,Sharif I,Gray GA,Sabin CA,Jenvey MC,Kolstoe SE,Thompson D,Wood SP

    更新日期:2006-04-27 00:00:00

  • Retinoblastoma-protein-dependent cell-cycle inhibition by the tumour suppressor p16.

    abstract::D-type cyclins, in association with the cyclin-dependent kinases Cdk4 or Cdk6, promote progression through the G1 phase of the cell cycle by phosphorylating the retinoblastoma protein (RB). The activities of Cdk4 and Cdk6 are constrained by inhibitors such as p16, the product of the CDKN2 gene on human chromosome 9p21...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/375503a0

    authors: Lukas J,Parry D,Aagaard L,Mann DJ,Bartkova J,Strauss M,Peters G,Bartek J

    更新日期:1995-06-08 00:00:00

  • Live imaging RNAi screen reveals genes essential for meiosis in mammalian oocytes.

    abstract::During fertilization, an egg and a sperm fuse to form a new embryo. Eggs develop from oocytes in a process called meiosis. Meiosis in human oocytes is highly error-prone, and defective eggs are the leading cause of pregnancy loss and several genetic disorders such as Down's syndrome. Which genes safeguard accurate pro...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/nature14568

    authors: Pfender S,Kuznetsov V,Pasternak M,Tischer T,Santhanam B,Schuh M

    更新日期:2015-08-13 00:00:00

  • A role for Lin28 in primordial germ-cell development and germ-cell malignancy.

    abstract::The rarity and inaccessibility of the earliest primordial germ cells (PGCs) in the mouse embryo thwart efforts to investigate molecular mechanisms of germ-cell specification. stella (also called Dppa3) marks the rare founder population of the germ lineage. Here we differentiate mouse embryonic stem cells carrying a st...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/nature08210

    authors: West JA,Viswanathan SR,Yabuuchi A,Cunniff K,Takeuchi A,Park IH,Sero JE,Zhu H,Perez-Atayde A,Frazier AL,Surani MA,Daley GQ

    更新日期:2009-08-13 00:00:00

  • Gravitationally redshifted absorption lines in the X-ray burst spectra of a neutron star.

    abstract::The fundamental properties of neutron stars provide a direct test of the equation of state of cold nuclear matter, a relationship between pressure and density that is determined by the physics of the strong interactions between the particles that constitute the star. The most straightforward method of determining thes...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/nature01159

    authors: Cottam J,Paerels F,Mendez M

    更新日期:2002-11-07 00:00:00

  • Electrical effects of spin density wave quantization and magnetic domain walls in chromium.

    abstract::The role of magnetic domains (and the walls between domains) in determining the electrical properties of ferromagnetic materials has been investigated in great detail for many years, not least because control over domains offers a means of manipulating electron spin to control charge transport in 'spintronic' devices....

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/nature06826

    authors: Kummamuru RK,Soh YA

    更新日期:2008-04-17 00:00:00

  • Catalysis by hen egg-white lysozyme proceeds via a covalent intermediate.

    abstract::Hen egg-white lysozyme (HEWL) was the first enzyme to have its three-dimensional structure determined by X-ray diffraction techniques. A catalytic mechanism, featuring a long-lived oxocarbenium-ion intermediate, was proposed on the basis of model-building studies. The 'Phillips' mechanism is widely held as the paradig...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/35090602

    authors: Vocadlo DJ,Davies GJ,Laine R,Withers SG

    更新日期:2001-08-23 00:00:00