Adhesion G protein-coupled receptors are activated by exposure of a cryptic tethered agonist.

Abstract:

:The large class of adhesion G protein-coupled receptors (aGPCRs) bind extracellular matrix or neighboring cell-surface ligands to regulate organ and tissue development through an unknown activation mechanism. We examined aGPCR activation using two prototypical aGPCRs, GPR56 and GPR110. Active dissociation of the noncovalently bound GPR56 or GPR110 extracellular domains (ECDs) from the respective seven-transmembrane (7TM) domains relieved an inhibitory influence and permitted both receptors to activate defined G protein subtypes. After ECD displacement, the newly revealed short N-terminal stalk regions of the 7TM domains were found to be essential for G protein activation. Synthetic peptides comprising these stalks potently activated GPR56 or GPR110 in vitro or in cells, demonstrating that the stalks comprise a tethered agonist that was encrypted within the ECD. Establishment of an aGPCR activation mechanism provides a rational platform for the development of aGPCR synthetic modulators that could find clinical utility toward aGPCR-directed disease.

authors

Stoveken HM,Hajduczok AG,Xu L,Tall GG

doi

10.1073/pnas.1421785112

subject

Has Abstract

pub_date

2015-05-12 00:00:00

pages

6194-9

issue

19

eissn

0027-8424

issn

1091-6490

pii

1421785112

journal_volume

112

pub_type

杂志文章
  • The 289-amino acid E1A protein of adenovirus binds zinc in a region that is important for trans-activation.

    abstract::The E1A gene of adenovirus type 5 encodes two major proteins of 289 and 243 amino acid residues, which are identical except that the larger protein has an internal stretch of 46 amino acids required for efficient trans-activation of early viral promoters. This domain contains a consensus zinc finger motif (Cys-Xaa2-Cy...

    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.85.17.6450

    authors: Culp JS,Webster LC,Friedman DJ,Smith CL,Huang WJ,Wu FY,Rosenberg M,Ricciardi RP

    更新日期:1988-09-01 00:00:00

  • Liver X receptor beta (LXRbeta): a link between beta-sitosterol and amyotrophic lateral sclerosis-Parkinson's dementia.

    abstract::Administration of beta-sitosterol (42 mg/kg per day) for 3 weeks to 8-month-old male LXRbeta-/- mice resulted in the death of motor neurons in the lumbar region of the spinal cord and loss of tyrosine hydroxylase-positive dopaminergic neurons in the substantia nigra. In mice at 5 months of age, beta-sitosterol had no ...

    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.0711599105

    authors: Kim HJ,Fan X,Gabbi C,Yakimchuk K,Parini P,Warner M,Gustafsson JA

    更新日期:2008-02-12 00:00:00

  • Adenosine diphosphate glucose pyrophosphatase: A plastidial phosphodiesterase that prevents starch biosynthesis.

    abstract::A distinct phosphodiesterasic activity (EC 3.1.4) was found in both mono- and dicotyledonous plants that catalyzes the hydrolytic breakdown of ADPglucose (ADPG) to produce equimolar amounts of glucose-1-phosphate and AMP. The enzyme responsible for this activity, referred to as ADPG pyrophosphatase (AGPPase), was puri...

    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.120168097

    authors: Rodriguez-López M,Baroja-Fernández E,Zandueta-Criado A,Pozueta-Romero J

    更新日期:2000-07-18 00:00:00

  • Rare somatic cells from human breast tissue exhibit extensive lineage plasticity.

    abstract::We identified cell surface markers associated with repression of p16(INK4a)/cyclin-dependent kinase inhibitor 2A(CDKN2A), a critical determinant in the acquisition of a plastic state. These cell surface markers allowed direct isolation of rare cells from healthy human breast tissue that exhibit extensive lineage plast...

    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.1218682110

    authors: Roy S,Gascard P,Dumont N,Zhao J,Pan D,Petrie S,Margeta M,Tlsty TD

    更新日期:2013-03-19 00:00:00

  • Protection of Cftr knockout mice from acute lung infection by a helper-dependent adenoviral vector expressing Cftr in airway epithelia.

    abstract::We developed a helper-dependent adenoviral vector for cystic fibrosis lung gene therapy. The vector expresses cystic fibrosis transmembrane conductance regulator (Cftr) using control elements from cytokeratin 18. The vector expressed properly localized CFTR in cultured cells and in the airway epithelia of mice. Cftr 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.2436478100

    authors: Koehler DR,Sajjan U,Chow YH,Martin B,Kent G,Tanswell AK,McKerlie C,Forstner JF,Hu J

    更新日期:2003-12-23 00:00:00

  • Different rat-derived transforming retroviruses code for an immunologically related intracellular phosphoprotein.

    abstract::Kirsten sarcoma virus (Ki-MSV) and Harvey sarcoma virus (Ha-MSV) are mouse-rat recombinant viruses that were originally isolated by experimental inoculation of rats with helper-independent mouse type C viruses. We have recently identified in cells transformed by Ki-MSV or Ha-MSV, a phosphoprotein, p21, coded for by Ki...

    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.76.7.3523

    authors: Young HA,Shih TY,Scolnick EM,Rasheed S,Gardner MB

    更新日期:1979-07-01 00:00:00

  • Protein design algorithms predict viable resistance to an experimental antifolate.

    abstract::Methods to accurately predict potential drug target mutations in response to early-stage leads could drive the design of more resilient first generation drug candidates. In this study, a structure-based protein design algorithm (K* in the OSPREY suite) was used to prospectively identify single-nucleotide polymorphisms...

    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.1411548112

    authors: Reeve SM,Gainza P,Frey KM,Georgiev I,Donald BR,Anderson AC

    更新日期:2015-01-20 00:00:00

  • Zebrafish type I collagen mutants faithfully recapitulate human type I collagenopathies.

    abstract::The type I collagenopathies are a group of heterogeneous connective tissue disorders, that are caused by mutations in the genes encoding type I collagen and include specific forms of osteogenesis imperfecta (OI) and the Ehlers-Danlos syndrome (EDS). These disorders present with a broad disease spectrum and large clini...

    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.1722200115

    authors: Gistelinck C,Kwon RY,Malfait F,Symoens S,Harris MP,Henke K,Hawkins MB,Fisher S,Sips P,Guillemyn B,Bek JW,Vermassen P,De Saffel H,Witten PE,Weis M,De Paepe A,Eyre DR,Willaert A,Coucke PJ

    更新日期:2018-08-21 00:00:00

  • Repurposing a peptide toxin from wasp venom into antiinfectives with dual antimicrobial and immunomodulatory properties.

    abstract::Novel antibiotics are urgently needed to combat multidrug-resistant pathogens. Venoms represent previously untapped sources of novel drugs. Here we repurposed mastoparan-L, the toxic active principle derived from the venom of the wasp Vespula lewisii, into synthetic antimicrobials. We engineered within its N 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.2012379117

    authors: Silva ON,Torres MDT,Cao J,Alves ESF,Rodrigues LV,Resende JM,Lião LM,Porto WF,Fensterseifer ICM,Lu TK,Franco OL,de la Fuente-Nunez C

    更新日期:2020-10-27 00:00:00

  • Sulfiredoxin-Peroxiredoxin IV axis promotes human lung cancer progression through modulation of specific phosphokinase signaling.

    abstract::Oxidative stress is known to cause tumorigenesis through induction of DNA and lipid damage. It also promotes cancer progression through a largely unknown mechanism. Sulfiredoxin (Srx) is a novel oxidative stress-induced antioxidant protein whose function in tumorigenesis and cancer progression has not been well studie...

    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.1013012108

    authors: Wei Q,Jiang H,Xiao Z,Baker A,Young MR,Veenstra TD,Colburn NH

    更新日期:2011-04-26 00:00:00

  • Effect of intravenous infusions of 12-O-tetradecanoylphorbol-13-acetate (TPA) in patients with myelocytic leukemia: preliminary studies on therapeutic efficacy and toxicity.

    abstract::Studies by several investigators have shown that 12-0-tetradecanoylphorbol-13-acetate (TPA) is an extraordinarily potent stimulator of differentiation of cultured human promyelocytic leukemia cells in vitro. In the present study, TPA was administered to humans by i.v. infusion without irreversible toxicity, and it was...

    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.95.9.5357

    authors: Han ZT,Zhu XX,Yang RY,Sun JZ,Tian GF,Liu XJ,Cao GS,Newmark HL,Conney AH,Chang RL

    更新日期:1998-04-28 00:00:00

  • Introducting of the 3-deoxy group in 3,6-dideoxyhexoses: a novel cofactor function for pyridoxamine-5'-phosphate.

    abstract::A cofactor needed for the reduction of CDP-4-keto-6-deoxy-D-glucose to CDP-4-keto-3,6-dideoxy D-glucose has been detected and purified. Its spectra in neutral, acid, and basic solutions, its behavior on thin-layer chromatography, and other properties led to its identification as pyridoxamine-5'-phosphate. Moreover, au...

    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.69.6.1625

    authors: Gonzalez-Porque P,Strominger JL

    更新日期:1972-06-01 00:00:00

  • Androgen-induced proliferative quiescence in prostate cancer cells: the role of AS3 as its mediator.

    abstract::In the prostate gland of adult mammals, most epithelial cells are in a state of proliferative quiescence. Androgens regulate this effect by inducing cell cycle arrest in the G(0)/G(1) phase. Potential mediators of this androgen-induced proliferative shutoff were identified by means of subtracted cDNA libraries. The ex...

    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.97.18.10185

    authors: Geck P,Maffini MV,Szelei J,Sonnenschein C,Soto AM

    更新日期:2000-08-29 00:00:00

  • Identification of a family of cAMP response element-binding protein coactivators by genome-scale functional analysis in mammalian cells.

    abstract::This report describes an unbiased method for systematically determining gene function in mammalian cells. A total of 20,704 predicted human full-length cDNAs were tested for induction of the IL-8 promoter. A number of genes, including those for cytokines, receptors, adapters, kinases, and transcription factors, were 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.1932773100

    authors: Iourgenko V,Zhang W,Mickanin C,Daly I,Jiang C,Hexham JM,Orth AP,Miraglia L,Meltzer J,Garza D,Chirn GW,McWhinnie E,Cohen D,Skelton J,Terry R,Yu Y,Bodian D,Buxton FP,Zhu J,Song C,Labow MA

    更新日期:2003-10-14 00:00:00

  • Molecular and electrophysiological characterization of a mechanosensitive channel expressed in the chloroplasts of Chlamydomonas.

    abstract::MscS is a mechanosensitive channel that is ubiquitous among bacteria. Recent progress in the genome projects has revealed that homologs of MscS are also present in eukaryotes, but whether they operate as ion channels is unknown. In this study we cloned MSC1, a homolog of MscS in Chlamydomonas, and examined its functio...

    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.0609996104

    authors: Nakayama Y,Fujiu K,Sokabe M,Yoshimura K

    更新日期:2007-04-03 00:00:00

  • Down-regulation of protein kinase C protects cerebellar granule neurons in primary culture from glutamate-induced neuronal death.

    abstract::Exposing primary cultures of cerebellar granule neurons to 100 nM phorbol 12-myristate 13-acetate (PMA) for 24 hr decreases the Ca2+/phosphatidylserine/diolein-dependent protein kinase C (PKC; ATP:protein phosphotransferase, EC 2.7.1.37) by approximately 90% in the 100,000 x g supernatant and pellet fractions of neuro...

    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.87.5.1983

    authors: Favaron M,Manev H,Siman R,Bertolino M,Szekely AM,DeErausquin G,Guidotti A,Costa E

    更新日期:1990-03-01 00:00:00

  • Analysis of 81 genes from 64 plastid genomes resolves relationships in angiosperms and identifies genome-scale evolutionary patterns.

    abstract::Angiosperms are the largest and most successful clade of land plants with >250,000 species distributed in nearly every terrestrial habitat. Many phylogenetic studies have been based on DNA sequences of one to several genes, but, despite decades of intensive efforts, relationships among early diverging lineages and sev...

    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.0709121104

    authors: Jansen RK,Cai Z,Raubeson LA,Daniell H,Depamphilis CW,Leebens-Mack J,Müller KF,Guisinger-Bellian M,Haberle RC,Hansen AK,Chumley TW,Lee SB,Peery R,McNeal JR,Kuehl JV,Boore JL

    更新日期:2007-12-04 00:00:00

  • Inversin relays Frizzled-8 signals to promote proximal pronephros development.

    abstract::Mutations of inversin cause type II nephronophthisis, an infantile autosomal recessive disease characterized by cystic kidney disease and developmental defects. Inversin regulates Wnt signaling and is required for convergent extension movements during early embryogenesis. We now show that Inversin is essential for Xen...

    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.1013070107

    authors: Lienkamp S,Ganner A,Boehlke C,Schmidt T,Arnold SJ,Schäfer T,Romaker D,Schuler J,Hoff S,Powelske C,Eifler A,Krönig C,Bullerkotte A,Nitschke R,Kuehn EW,Kim E,Burkhardt H,Brox T,Ronneberger O,Gloy J,Walz G

    更新日期:2010-11-23 00:00:00

  • Molecular basis for AUXIN RESPONSE FACTOR protein interaction and the control of auxin response repression.

    abstract::In plants, the AUXIN RESPONSE FACTOR (ARF) transcription factor family regulates gene expression in response to auxin. In the absence of auxin, ARF transcription factors are repressed by interaction with AUXIN/INDOLE 3-ACETIC ACID (Aux/IAA) proteins. Although the C termini of ARF and Aux/IAA proteins facilitate their ...

    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.1400074111

    authors: Korasick DA,Westfall CS,Lee SG,Nanao MH,Dumas R,Hagen G,Guilfoyle TJ,Jez JM,Strader LC

    更新日期:2014-04-08 00:00:00

  • Bipolar switching by HCN voltage sensor underlies hyperpolarization activation.

    abstract::Despite sharing a common architecture with archetypal voltage-gated ion channels (VGICs), hyperpolarization- and cAMP-activated ion (HCN) channels open upon hyperpolarization rather than depolarization. The basic motions of the voltage sensor and pore gates are conserved, implying that these domains are inversely coup...

    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.1816724116

    authors: Cowgill J,Klenchin VA,Alvarez-Baron C,Tewari D,Blair A,Chanda B

    更新日期:2019-01-08 00:00:00

  • FM dyes enter via a store-operated calcium channel and modify calcium signaling of cultured astrocytes.

    abstract::The amphiphilic fluorescent styryl pyridinium dyes FM1-43 and FM4-64 are used to probe activity-dependent synaptic vesicle cycling in neurons. Cultured astrocytes can internalize FM1-43 and FM4-64 inside vesicles but their uptake is insensitive to the elevation of cytosolic calcium (Ca(2+)) concentration and the under...

    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.0909109106

    authors: Li D,Hérault K,Oheim M,Ropert N

    更新日期:2009-12-22 00:00:00

  • The modular architecture of protein-protein binding interfaces.

    abstract::Protein-protein interactions are essential for life. Yet, our understanding of the general principles governing binding is not complete. In the present study, we show that the interface between proteins is built in a modular fashion; each module is comprised of a number of closely interacting residues, with few intera...

    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.0407280102

    authors: Reichmann D,Rahat O,Albeck S,Meged R,Dym O,Schreiber G

    更新日期:2005-01-04 00:00:00

  • Clonal analysis of proliferation and differentiation of paired daughter cells: action of granulocyte-macrophage colony-stimulating factor on granulocyte-macrophage precursors.

    abstract::Mouse granulocyte-macrophage progenitor cells were stimulated to divide by the granulocyte-macrophage colony-stimulating factor (GM-CSF). The two daughter cells were separated; one daughter was transferred to medium containing a high concentration of GM-CSF, the other to medium containing a low concentration. Daughter...

    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.77.9.5327

    authors: Metcalf D

    更新日期:1980-09-01 00:00:00

  • 3T3 fibroblasts induce cloned interleukin 3-dependent mouse mast cells to resemble connective tissue mast cells in granular constituency.

    abstract::As assessed by ultrastructure, histochemical staining, and T-cell dependency, in vitro-differentiated inter-leukin 3-dependent mouse mast cells are comparable to the mast cells that reside in the gastrointestinal mucosa but not in the skin or the serosal cavity of the mouse. We now demonstrate that when cloned interle...

    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.85.2.569

    authors: Dayton ET,Pharr P,Ogawa M,Serafin WE,Austen KF,Levi-Schaffer F,Stevens RL

    更新日期:1988-01-01 00:00:00

  • A chimeric adenovirus vector encoding reovirus attachment protein sigma1 targets cells expressing junctional adhesion molecule 1.

    abstract::The utility of adenovirus (Ad) vectors for gene transduction can be limited by receptor specificity. We developed a gene-delivery vehicle in which the potent Ad5 vector was genetically reengineered to display the mucosal-targeting sigma1 protein of reovirus type 3 Dearing (T3D). A sigma1 construct containing all but 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.0400542101

    authors: Mercier GT,Campbell JA,Chappell JD,Stehle T,Dermody TS,Barry MA

    更新日期:2004-04-20 00:00:00

  • phiX174 DNA-dependent DNA synthesis in vitro: requirement for P1 ban protein in dnaB mutant extracts of Escherichia coli.

    abstract::Ammonium sulfate fractionation of crude extracts of E. coli yields a soluble enzyme fraction (about 25-fold purification) that catalyzes the conversion of phiX174 single-stranded DNA to duplex DNA. The reaction is rifampicin-resistant, requires single-stranded DNA, Mg++, deoxynucleoside triphosphates, and ATP, and 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.72.10.3907

    authors: Schuster H,Mikolajczyk M,Rohrschneider J,Geschke B

    更新日期:1975-10-01 00:00:00

  • Inhibition of actomyosin ATPase by vanadate.

    abstract::Actin-myosin subfragment-1 (SF-1) or actin-heavy meromyosin is dissociated by the binding of ADP and vanadate (Vi) under conditions such that ADP alone does not dissociate the complex. The association constant of the stable complex M.ADP.Vi, in which M indicates myosin [Goodno, C. C. (1979) Proc. Natl. Acad. Sci. USA ...

    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.79.1.21

    authors: Goodno CC,Taylor EW

    更新日期:1982-01-01 00:00:00

  • Reconstitution of p53-ubiquitinylation reactions from purified components: the role of human ubiquitin-conjugating enzyme UBC4 and E6-associated protein (E6AP).

    abstract::The E6 protein of the high-risk human papillomaviruses inactivates the tumor suppressor protein p53 by stimulating its ubiquitinylation and subsequent degradation. Ubiquitinylation is a multistep process involving a ubiquitin-activating enzyme, one of many distinct ubiquitin-conjugating enzymes, and in certain cases, ...

    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.92.8.3264

    authors: Rolfe M,Beer-Romero P,Glass S,Eckstein J,Berdo I,Theodoras A,Pagano M,Draetta G

    更新日期:1995-04-11 00:00:00

  • Deficiency of transcription factor RelB perturbs myeloid and DC development by hematopoietic-extrinsic mechanisms.

    abstract::RelB is an NF-κB family transcription factor activated in the noncanonical pathway downstream of NF-κB-inducing kinase (NIK) and TNF receptor family members including lymphotoxin-β receptor (LTβR) and CD40. Early analysis suggested that RelB is required for classical dendritic cell (cDC) development based on a severe ...

    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.1619863114

    authors: Briseño CG,Gargaro M,Durai V,Davidson JT,Theisen DJ,Anderson DA 3rd,Novack DV,Murphy TL,Murphy KM

    更新日期:2017-04-11 00:00:00

  • Anthropogenic strath terrace formation caused by reduced sediment retention.

    abstract::Across North America, human activities have been shown to cause river incision into unconsolidated alluvium. Human-caused erosion through bedrock, however, has only been observed in local and isolated outcrops. Here, we test whether splash-dam logging, which decreased in-stream alluvial cover by removing much of the 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.1814627116

    authors: Schanz SA,Montgomery DR,Collins BD

    更新日期:2019-04-30 00:00:00