A constitutively active mutant beta 2-adrenergic receptor is constitutively desensitized and phosphorylated.

Abstract:

:The beta 2-adrenergic receptor (beta 2AR) can be constitutively activated by mutations in the third intracellular loop. Whereas the wild-type receptor exists predominantly in an inactive conformation (R) in the absence of agonist, the mutant receptor appears to spontaneously adopt an active conformation (R*). We now demonstrate that not only is the mutant beta 2AR constitutively active, it is also constitutively desensitized and down-regulated. To assess whether the mutant receptor can constitutively engage a known element of the cellular desensitization machinery, the receptor was purified and reconstituted into phospholipid vesicles. These preparations retained the essential properties of the constitutively active mutant receptor: agonist-independent activity [to stimulate guanine nucleotide-binding protein (Gs)-GTPase] and agonist-specific increase in binding affinity. Moreover, the purified mutant receptor, in the absence of agonist, was phosphorylated by recombinant beta AR-specific kinase (beta ARK) in a fashion comparable to the agonist-occupied wild-type receptor. Thus, the conformation of the mutated receptor is equivalent to the active conformation (R*), which stimulates Gs protein and is identical to the beta ARK substrate.

authors

Pei G,Samama P,Lohse M,Wang M,Codina J,Lefkowitz RJ

doi

10.1073/pnas.91.7.2699

subject

Has Abstract

pub_date

1994-03-29 00:00:00

pages

2699-702

issue

7

eissn

0027-8424

issn

1091-6490

journal_volume

91

pub_type

杂志文章
  • A DNA-mediated transformation system for Dictyostelium discoideum.

    abstract::We have established a transformation system for Dictyostelium discoideum. The transformation vector contains the protein coding region of the Tn5 neomycin resistance gene fused to the proposed promoter of the Dictyostelium actin 8 gene; the vector also contains a sequence that acts as an autonomously replicating seque...

    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.79.23.7356

    authors: Hirth KP,Edwards CA,Firtel RA

    更新日期:1982-12-01 00:00:00

  • The immune response attenuates growth and nutrient storage in Drosophila by reducing insulin signaling.

    abstract::Innate immunity is the primary and most ancient defense against infection. Although critical to survival, coordinating protection against a foreign organism is energetically costly, creating the need to reallocate substrates from nonessential functions, such as growth and nutrient storage. However, the mechanism by wh...

    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.0906749106

    authors: DiAngelo JR,Bland ML,Bambina S,Cherry S,Birnbaum MJ

    更新日期:2009-12-08 00:00:00

  • Infectious hepatitis B virus from cloned DNA of known nucleotide sequence.

    abstract::The infectivity of cloned hepatitis B viral DNA (HBV) has been tested in chimpanzees to identify a fully functional HBV genome and to assess the risk associated with its handling. Only one of two HBV DNA sequence variants tested was shown to be infectious. "Clone purified" virus of predicted nucleotide sequence was pr...

    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.82.3.891

    authors: Will H,Cattaneo R,Darai G,Deinhardt F,Schellekens H,Schaller H

    更新日期:1985-02-01 00:00:00

  • A manganese transporter, BB0219 (BmtA), is required for virulence by the Lyme disease spirochete, Borrelia burgdorferi.

    abstract::Borrelia burgdorferi (Bb), the causative agent of Lyme disease, is transmitted to mammalian hosts through an arthropod (tick) vector. To establish infection, Bb must acquire essential nutrients, including transition metals, from its mammalian and tick hosts. Thus far, no metal transporter has been identified in Bb. He...

    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.0812999106

    authors: Ouyang Z,He M,Oman T,Yang XF,Norgard MV

    更新日期:2009-03-03 00:00:00

  • Type II regulatory subunits are not required for the anchoring-dependent modulation of Ca2+ channel activity by cAMP-dependent protein kinase.

    abstract::Preferential phosphorylation of specific proteins by cAMP-dependent protein kinase (PKA) may be mediated in part by the anchoring of PKA to a family of A-kinase anchor proteins (AKAPs) positioned in close proximity to target proteins. This interaction is thought to depend on binding of the type II regulatory (RII) sub...

    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.94.20.11067

    authors: Burton KA,Johnson BD,Hausken ZE,Westenbroek RE,Idzerda RL,Scheuer T,Scott JD,Catterall WA,McKnight GS

    更新日期:1997-09-30 00:00:00

  • Autogenous suppression of an opal mutation in the gene encoding peptide chain release factor 2.

    abstract::The peptide chain release factor 2 (RF2) gene, prfB, was cloned from Salmonella typhimurium by DNA hybridization using the Escherichia coli prfB probe. The nucleotide and amino acid sequences of prfB are 87.0% and 95.6% homologous between E. coli and S. typhimurium, respectively, including an in-frame premature UGA st...

    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.87.21.8432

    authors: Kawakami K,Nakamura Y

    更新日期:1990-11-01 00:00:00

  • Efficient genome engineering in human pluripotent stem cells using Cas9 from Neisseria meningitidis.

    abstract::Genome engineering in human pluripotent stem cells (hPSCs) holds great promise for biomedical research and regenerative medicine. Recently, an RNA-guided, DNA-cleaving interference pathway from bacteria [the type II clustered, regularly interspaced, short palindromic repeats (CRISPR)-CRISPR-associated (Cas) pathway] h...

    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.1313587110

    authors: Hou Z,Zhang Y,Propson NE,Howden SE,Chu LF,Sontheimer EJ,Thomson JA

    更新日期:2013-09-24 00:00:00

  • Early tertiary elephant-shrews from Egypt and the origin of the Macroscelidea.

    abstract::Recent expeditions to the Fayum Depression, Egypt, have made possible the discovery of mandibles and a maxilla of a new genus and species of late Eocene elephant-shrew as well as initial evidence of the upper dentition of the early Oligocene taxon Metoldobotes. These fossils demonstrate that macroscelideans underwent ...

    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.88.21.9734

    authors: Simons EL,Holroyd PA,Bown TM

    更新日期:1991-11-01 00:00:00

  • Agonist-induced formation of unproductive receptor-G12 complexes.

    abstract::G proteins are activated when they associate with G protein-coupled receptors (GPCRs), often in response to agonist-mediated receptor activation. It is generally thought that agonist-induced receptor-G protein association necessarily promotes G protein activation and, conversely, that activated GPCRs do not interact w...

    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.2003787117

    authors: Okashah N,Wright SC,Kawakami K,Mathiasen S,Zhou J,Lu S,Javitch JA,Inoue A,Bouvier M,Lambert NA

    更新日期:2020-09-01 00:00:00

  • N-Nitroso-N-methylurea elicits mammary cancer in resistant and sensitive rat strains.

    abstract::A single intravenous (i.v.) injection of the water-soluble mammary carcinogen N-nitroso-N-methylurea (NMU; 35 mg/kg of body weight) elicited cancer of the breast in young female rats of two strains in the following incidence: Long-Evans strain, 4%; Sprague-Dawley strain, 70%. In sisters of these rats, a set of 5 i.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.78.2.1185

    authors: Huggins CB,Ueda N,Wiessler M

    更新日期:1981-02-01 00:00:00

  • Anisotropic particles align perpendicular to the flow direction in narrow microchannels.

    abstract::The flow orientation of anisotropic particles through narrow channels is of importance in many fields, ranging from the spinning and molding of fibers to the flow of cells and proteins through thin capillaries. It is commonly assumed that anisotropic particles align parallel to the flow direction. When flowing through...

    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.1219340110

    authors: Trebbin M,Steinhauser D,Perlich J,Buffet A,Roth SV,Zimmermann W,Thiele J,Förster S

    更新日期:2013-04-23 00:00:00

  • Mechanism of integrating foreign DNA during transformation of Bacillus subtilis.

    abstract::Genes encoding thymidylate synthetase from Bacillus subtilis bacteriophages were cloned in Escherichia coli. Chimeric plasmids pCD1 and pCD3 were constructed from site-specific endonuclease digests of bacteriophage phi3T DNA cloned in pMB9 in E. coli. Similar cloning techniques with bacteriophage beta22 DNA yielded 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.75.8.3664

    authors: Duncan CH,Wilson GA,Young FE

    更新日期:1978-08-01 00:00:00

  • Yeast RNA polymerase II initiation factor e: isolation and identification as the functional counterpart of human transcription factor IIB.

    abstract::Yeast RNA polymerase II initiation factor e was purified to homogeneity and identified by biochemical criteria as the counterpart of human transcription factor IIB. Factor e was essential for initiation of transcription from yeast and mammalian promoters in a reconstituted yeast transcription system. Activity resided ...

    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.89.23.11292

    authors: Tschochner H,Sayre MH,Flanagan PM,Feaver WJ,Kornberg RD

    更新日期:1992-12-01 00:00:00

  • Circadian clock control of eIF2α phosphorylation is necessary for rhythmic translation initiation.

    abstract::The circadian clock in eukaryotes controls transcriptional and posttranscriptional events, including regulation of the levels and phosphorylation state of translation factors. However, the mechanisms underlying clock control of translation initiation, and the impact of this potential regulation on rhythmic protein syn...

    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.1918459117

    authors: Karki S,Castillo K,Ding Z,Kerr O,Lamb TM,Wu C,Sachs MS,Bell-Pedersen D

    更新日期:2020-05-19 00:00:00

  • Missense and silent tau gene mutations cause frontotemporal dementia with parkinsonism-chromosome 17 type, by affecting multiple alternative RNA splicing regulatory elements.

    abstract::Frontotemporal dementia with parkinsonism, chromosome 17 type (FTDP-17) is caused by mutations in the tau gene, and the signature lesions of FTDP-17 are filamentous tau inclusions. Tau mutations may be pathogenic either by altering protein function or gene regulation. Here we show that missense, silent, and intronic 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.96.10.5598

    authors: D'Souza I,Poorkaj P,Hong M,Nochlin D,Lee VM,Bird TD,Schellenberg GD

    更新日期:1999-05-11 00:00:00

  • Structures of eukaryotic ribonucleotide reductase I define gemcitabine diphosphate binding and subunit assembly.

    abstract::Ribonucleotide reductase (RNR) catalyzes the conversion of nucleoside diphosphates to deoxynucleoside diphosphates. Crucial for rapidly dividing cells, RNR is a target for cancer therapy. In eukaryotes, RNR comprises a heterooligomer of alpha(2) and beta(2) subunits. Rnr1, the alpha subunit, contains regulatory and ca...

    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.0600440103

    authors: Xu H,Faber C,Uchiki T,Racca J,Dealwis C

    更新日期:2006-03-14 00:00:00

  • Intersection of FOXO- and RUNX1-mediated gene expression programs in single breast epithelial cells during morphogenesis and tumor progression.

    abstract::Gene expression networks are complicated by the assortment of regulatory factors that bind DNA and modulate transcription combinatorially. Single-cell measurements can reveal biological mechanisms hidden by population averages, but their value has not been fully explored in the context of mRNA regulation. Here, we ada...

    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.1103423108

    authors: Wang L,Brugge JS,Janes KA

    更新日期:2011-10-04 00:00:00

  • Representation of stable social dominance relations by human infants.

    abstract::What are the origins of humans' capacity to represent social relations? We approached this question by studying human infants' understanding of social dominance as a stable relation. We presented infants with interactions between animated agents in conflict situations. Studies 1 and 2 targeted expectations of stabilit...

    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.1113194109

    authors: Mascaro O,Csibra G

    更新日期:2012-05-01 00:00:00

  • Vacuolar H(+)-pumping ATPase variable transport coupling ratio controlled by pH.

    abstract::The eukaryote endomembrane system contains a class of H(+)-pumping ATPase (H(+)-ATPases) of the vacuolar type (V-ATPases) that are responsible for the acidification of organelles. Their action is critical to numerous physiological processes, but the regulatory mechanisms that may control activity are not yet fully und...

    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.91.18.8547

    authors: Davies JM,Hunt I,Sanders D

    更新日期:1994-08-30 00:00:00

  • Reactive nanostructured membranes for water purification.

    abstract::Many current treatments for the reclamation of contaminated water sources are chemical-intensive, energy-intensive, and/or require posttreatment due to unwanted by-product formation. We demonstrate that through the integration of nanostructured materials, enzymatic catalysis, and iron-catalyzed free radical reactions ...

    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.1101144108

    authors: Lewis SR,Datta S,Gui M,Coker EL,Huggins FE,Daunert S,Bachas L,Bhattacharyya D

    更新日期:2011-05-24 00:00:00

  • Reassessing the atmospheric oxidation mechanism of toluene.

    abstract::Photochemical oxidation of aromatic hydrocarbons leads to tropospheric ozone and secondary organic aerosol (SOA) formation, with profound implications for air quality, human health, and climate. Toluene is the most abundant aromatic compound under urban environments, but its detailed chemical oxidation mechanism remai...

    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.1705463114

    authors: Ji Y,Zhao J,Terazono H,Misawa K,Levitt NP,Li Y,Lin Y,Peng J,Wang Y,Duan L,Pan B,Zhang F,Feng X,An T,Marrero-Ortiz W,Secrest J,Zhang AL,Shibuya K,Molina MJ,Zhang R

    更新日期:2017-08-01 00:00:00

  • An infectious arterivirus cDNA clone: identification of a replicase point mutation that abolishes discontinuous mRNA transcription.

    abstract::Equine arteritis virus (EAV) is a positive-strand RNA virus that uses a discontinuous transcription mechanism to generate a nested set of six subgenomic mRNAs from which its structural genes are expressed. A stable bacterial plasmid (pEAV030) containing a full-length cDNA copy of the 12.7-kb EAV genome was constructed...

    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.94.3.991

    authors: van Dinten LC,den Boon JA,Wassenaar AL,Spaan WJ,Snijder EJ

    更新日期:1997-02-04 00:00:00

  • Multilinear Littlewood-Paley estimates with applications to partial differential equations.

    abstract::We obtain a collection of multilinear Littlewood-Paley estimates, which we then apply to two problems in partial differential equations. The first problem is the estimation of the square root of an elliptic operator in divergence form, and the second is the estimation of solutions to the Cauchy problem for nondivergen...

    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.79.18.5746

    authors: Fabes EB,Jerison DS,Kenig CE

    更新日期:1982-09-01 00:00:00

  • Elevated auxin biosynthesis and transport underlie high vein density in C4 leaves.

    abstract::High vein density, a distinctive trait of C4 leaves, is central to both C3-to-C4 evolution and conversion of C3 to C4-like crops. We tested the hypothesis that high vein density in C4 leaves is due to elevated auxin biosynthesis and transport in developing leaves. Up-regulation of genes in auxin biosynthesis pathways ...

    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.1709171114

    authors: Huang CF,Yu CP,Wu YH,Lu MJ,Tu SL,Wu SH,Shiu SH,Ku MSB,Li WH

    更新日期:2017-08-15 00:00:00

  • Genomic analysis of uncultured marine viral communities.

    abstract::Viruses are the most common biological entities in the oceans by an order of magnitude. However, very little is known about their diversity. Here we report a genomic analysis of two uncultured marine viral communities. Over 65% of the sequences were not significantly similar to previously reported sequences, suggestin...

    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.202488399

    authors: Breitbart M,Salamon P,Andresen B,Mahaffy JM,Segall AM,Mead D,Azam F,Rohwer F

    更新日期:2002-10-29 00:00:00

  • Genome fragment of Wolbachia endosymbiont transferred to X chromosome of host insect.

    abstract::The adzuki bean beetle, Callosobruchus chinensis, is triple-infected with distinct lineages of Wolbachia endosymbiont, wBruCon, wBruOri, and wBruAus, which were identified by their wsp (Wolbachia surface protein) gene sequences. Whereas wBruCon and wBruOri caused cytoplasmic incompatibility of the host insect, wBruAus...

    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.222228199

    authors: Kondo N,Nikoh N,Ijichi N,Shimada M,Fukatsu T

    更新日期:2002-10-29 00:00:00

  • Biochemical basis for dominant mutations in the Saccharomyces cerevisiae MSH6 gene.

    abstract::Here, the ATP-binding, ATP hydrolysis, mispair-binding, sliding clamp formation, and Mlh1-Pms1 complex interaction properties of dominant mutant Msh2-Msh6 complexes have been characterized. The results demonstrate two mechanisms for dominance. In one, seen with the Msh6-S1036P and Msh6-G1067D mutant complexes, the mut...

    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.0510078103

    authors: Hess MT,Mendillo ML,Mazur DJ,Kolodner RD

    更新日期:2006-01-17 00:00:00

  • Yeast ADA2 protein binds to the VP16 protein activation domain and activates transcription.

    abstract::Previously it was shown that yeast ADA2 protein is necessary for the full activity of some activation domains, such as VP16 and GCN4, in vivo and in vitro. These results suggest that ADA2 protein functions as a transcriptional coactivator or adaptor that bridges the interaction between certain acidic activation domain...

    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.91.24.11665

    authors: Silverman N,Agapite J,Guarente L

    更新日期:1994-11-22 00:00:00

  • Structure of RavA MoxR AAA+ protein reveals the design principles of a molecular cage modulating the inducible lysine decarboxylase activity.

    abstract::The MoxR family of AAA+ ATPases is widespread throughout bacteria and archaea but remains poorly characterized. We recently found that the Escherichia coli MoxR protein, RavA (Regulatory ATPase variant A), tightly interacts with the inducible lysine decarboxylase, LdcI/CadA, to form a unique cage-like structure. Here,...

    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.1009092107

    authors: El Bakkouri M,Gutsche I,Kanjee U,Zhao B,Yu M,Goret G,Schoehn G,Burmeister WP,Houry WA

    更新日期:2010-12-28 00:00:00

  • Species interactions limit the occurrence of urban-adapted birds in cities.

    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

    authors: Martin PR,Bonier F

    更新日期:2018-12-04 00:00:00