Abstract:
:Most guanine nucleotide binding protein (G protein)-coupled receptors have a conserved cysteine in the C-terminal cytoplasmic tail near the seventh transmembrane spanning region. This cysteine is known to be palmitoylated in rhodopsin, the beta 2-adrenergic receptor (beta 2AR) and the alpha 2A-adrenergic receptor (alpha 2AAR). For the beta 2AR, this cysteine has been shown to be important for stimulatory G protein (Gs) coupling and agonist-promoted desensitization. For the alpha 2AAR (human alpha 2 C10) palmitoylation occurs at Cys-442, but it is not known what function such fatty acid acylation subserves. The closely related alpha 2CAR subtype denoted alpha 2C4 lacks a cysteine in this region and has different G-protein-coupling characteristics and agonist regulatory properties as compared to alpha 2C10. To assess the role of the palmitoylcysteine in alpha 2AR function, we constructed a mutated alpha 2C10 having a phenylalanine (the analogous amino acid in the alpha 2C4 in this position) substituted for Cys-442, denoted alpha 2C10(Phe-442), and expressed this along with wild-type alpha 2C10 and alpha 2C4 in CHO cells. Functional coupling to inhibitory G protein (Gi) and to Gs was identical between wild-type alpha 2C10 and alpha 2C10(Phe-442). Agonist-promoted desensitization of both the Gi and Gs-mediated pathways was also found to be unaffected by this mutation. Cellular trafficking induced by agonist exposure was evaluated by delineation of intracellular (sequestered) versus cell surface receptors and by determination of net receptor loss. Mutation of Cys-442 did not alter the extent or rate of agonist-promoted sequestration induced by agonists or the recovery from sequestration. However, the downregulation of receptor number after prolonged agonist exposure was completely abolished by this mutation and converted alpha 2C10 to an alpha 2C4 phenotype in regard to this adaptive response. Another mutated alpha 2C10, in which Cys-442 was replaced by alanine, also failed to downregulate. Thus, the function of this cytoplasmic palmitoylcysteine is distinctly different between the alpha 2AR and other G-protein-coupled receptors such as the beta 2AR and rhodopsin, and this suggests that this molecular attribute may subserve diverse roles among members of this family of receptors. For the alpha 2ARs, this may represent an evolved feature that provides for differing needs for regulation of the alpha 2C10 and alpha 2C4 subtypes by agonist.
journal_name
Proc Natl Acad Sci U S Aauthors
Eason MG,Jacinto MT,Theiss CT,Liggett SBdoi
10.1073/pnas.91.23.11178subject
Has Abstractpub_date
1994-11-08 00:00:00pages
11178-82issue
23eissn
0027-8424issn
1091-6490journal_volume
91pub_type
杂志文章abstract::Rod-shaped "ghosts" that are free of murein have been isolated from E. coli. The shape of these "ghosts" is maintained by a unit membrane soluble in sodium dodecyl sulfate. Ghosts consist of about 20-30% phospholipid (almost exclusively phosphatidylethanolamine) and 50-60% protein; a large fraction of the remaining ma...
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.70.7.2033
更新日期:1973-07-01 00:00:00
abstract::Diverse motivations for preserving nature both inspire and hinder its conservation. Optimal conservation strategies may differ radically depending on the objective. For example, creating nature reserves may prevent extinctions through protecting severely threatened species, whereas incentivizing farmland hedgerows may...
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.1504788112
更新日期:2015-09-01 00:00:00
abstract::We used positron emission tomography (PET) to examine the role of the hippocampal formation in implicit and explicit memory. Human volunteers studied a list of familiar words, and then they either provided the first word that came to mind in response to three-letter cues (implicit memory) or tried to recall studied wo...
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.93.1.321
更新日期:1996-01-09 00:00:00
abstract::The complex prokaryote, Myxococcus xanthus, undergoes a program of multicellular development when starved for nutrients, culminating in sporulation. M. xanthus makes MglA, a 22-kDa, soluble protein that is required for both multicellular development and gliding motility. MglA is similar in sequence to the Saccharomyce...
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.94.18.9881
更新日期:1997-09-02 00:00:00
abstract::The capacity of Shigella to spread within the cytosol of infected epithelial cells and to infect adjacent cells is critical for the development of infection foci, which lead to mucosal abscesses. Shigella is a nonmotile microorganism that appears to utilize host cell microfilaments to generate intra- as well as interc...
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.86.10.3867
更新日期:1989-05-01 00:00:00
abstract::Coherent anti-Stokes Raman scattering (CARS) spectra are reported for flavin adenine dinucleotide (FAD) and glucose oxidase (beta-D-glucose:oxygen 1-oxidoreductase; EC 1.1.3.4), in resonance with the 450 nm flavin absorption band. Several isoalloxazine ring modes were observed (1635, 1584, 1507, 1416, and 1359 cm(-1))...
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.74.10.4146
更新日期:1977-10-01 00:00:00
abstract::Niemann-Pick type C disease (NP-C) is an inherited neurovisceral lipid storage disorder characterized by progressive neurodegeneration. Most cases of NP-C result from inactivating mutations of NPC1, a recently identified member of a family of genes encoding membrane-bound proteins containing putative sterol sensing do...
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.96.4.1657
更新日期:1999-02-16 00:00:00
abstract::We created a high-throughput modality of photoactivated localization microscopy (PALM) that enables automated 3D PALM imaging of hundreds of synchronized bacteria during all stages of the cell cycle. We used high-throughput PALM to investigate the nanoscale organization of the bacterial cell division protein FtsZ in l...
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.1313368111
更新日期:2014-03-25 00:00:00
abstract::The constant heavy chain (CH1) domain affects antibody affinity and fine specificity, challenging the paradigm that only variable regions contribute to antigen binding. To investigate the role of the CH1 domain, we constructed IgA2 from the broadly neutralizing anti-HIV-1 2F5 IgG1, and compared 2F5 IgA2 and IgG bindin...
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.1200024109
更新日期:2012-07-31 00:00:00
abstract::The "false thumb" of pandas is a carpal bone, the radial sesamoid, which has been enlarged and functions as an opposable thumb. If the giant panda (Ailuropoda melanoleuca) and the red panda (Ailurus fulgens) are not closely related, their sharing of this adaptation implies a remarkable convergence. The discovery of 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.0504899102
更新日期:2006-01-10 00:00:00
abstract::A serpin was identified in normal mammary gland by differential cDNA sequencing. In situ hybridization has detected this serpin exclusively in the myoepithelial cells on the normal and noninvasive mammary epithelial side of the basement membrane and thus was named myoepithelium-derived serine proteinase inhibitor (MEP...
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.96.7.3700
更新日期:1999-03-30 00:00:00
abstract::Incubation of physiological concentrations of 125I-labeled insulin with liver membranes in the presence of anti-insulin IgG results in a 7- to 15-fold increase in the specific binding of the hormone. The low-affinity/high-capacity binding sites are replaced by an apparently homogeneous class of high-affinity sites, an...
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.76.6.2720
更新日期:1979-06-01 00:00:00
abstract::Homopyrimidine oligonucleotides bind to the major groove of a complementary homopyrimidine.homopurine stretch by triple helix formation. The bla gene from transposon Tn3 contains a homopyrimidine.homopurine sequence of 13 base pairs located just downstream of the RNA polymerase binding site. A 13-mer homopyrimidine ol...
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.89.2.504
更新日期:1992-01-15 00:00:00
abstract::Glycosyl phosphates are shown to be activated to stereospecific nucleophilic substitution reactions by precisely tailored bis-thiourea catalysts. Enhanced reactivity and scope is observed with phosphate relative to chloride leaving groups. Stronger binding (Km) to the H-bond donor and enhanced reactivity of the comple...
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.1811186116
更新日期:2019-01-02 00:00:00
abstract::Immune responses of the malaria vector mosquito Anopheles gambiae were monitored systematically by the induced expression of five RNA markers after infection challenge. One newly isolated marker encodes a homologue of the moth Gram-negative bacteria-binding protein (GNBP), and another corresponds to a serine protease-...
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.94.21.11508
更新日期:1997-10-14 00:00:00
abstract::The importance of founder events in promoting evolutionary changes on islands has been a subject of long-running controversy. Resolution of this debate has been hindered by a lack of empirical evidence from naturally founded island populations. Here we undertake a genetic analysis of a series of historically documente...
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.102583399
更新日期:2002-06-11 00:00:00
abstract::The effect of plasmin-derived fibrinogen fragments on the biosynthesis of fibrinogen was investigated in cultured monolayers of rat hepatocytes. Incubating the cells with several concentrations of either fibrinogen or fibrin fragment D or E had no effect on the synthesis and secretion of fibrinogen by these cells. How...
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.79.5.1530
更新日期:1982-03-01 00:00:00
abstract::Transmission electron microscope images were obtained of fractions of poly(1-tetradecene sulfone) and poly(cyclohexene sulfone) cast from very dilute solutions (0.007%, wt/vol) and rapidly freeze-dried on a mica surface. The samples were then vertically platinum-carbon (Pt-C) replicated with 9 +/- 0.3-A Pt-C and held ...
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.89.17.7991
更新日期:1992-09-01 00:00:00
abstract::The gene encoding latent-infection membrane protein 1 (LMP1) was specifically mutated in Epstein-Barr virus (EBV) recombinants by inserting a nonsense linker after codon 9 or codon 84 or into an intron 186 bp 3' to the latter insertion site. EBV recombinants with the LMP1 intron mutation were wild type for LMP1 expres...
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.90.19.9150
更新日期:1993-10-01 00:00:00
abstract::A study of behavior and structure indicates that highly eusocial behavior arose twice in the bees--i.e., in the stingless bees (Meliponinae) and in the honeybees (Apinae). Morphological features demonstrate the distinctiveness of these two groups and the relationship of the latter to bumblebees (Bombini) and orchid be...
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.74.3.1135
更新日期:1977-03-01 00:00:00
abstract::We have determined the nucleotide sequences of cDNAs encoding the precursor of the beta subunit of rat lutropin, a polypeptide hormone that regulates gonadal function, including the development of gametes and the production of steroid sex hormones. The cDNAs were prepared from poly(A)+ RNA derived from the pituitary g...
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.80.15.4649
更新日期:1983-08-01 00:00:00
abstract::[14C]Naphthalene was given orally to rats with cannulated bile ducts and to germ-free rats. Bile and urine from the cannulated rats and urine from the germ-free rats contained no radioactive 1,2-dihydro-1-hydroxy-2-methylthionaphthalene and only trace amounts of radioactive naphthols or naphthol conjugates. Urine of c...
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.82.3.668
更新日期:1985-02-01 00:00:00
abstract::DNA fragments encoding the mouse steroid 21-hydroxylase (C21 or Cyp21A1) gene are de novo methylated when introduced into the mouse adrenocortical tumor cell line Y1 by DNA-mediated gene transfer. Although CCGG sequences within the C21 gene are de novo methylated, CCGG sites within flanking vector sequences, other mam...
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.86.18.6853
更新日期:1989-09-01 00:00:00
abstract::Antischizophrenic neuroleptic drugs of the diphenylbutylpiperidine class, which includes pimozide, fluspirilene, penfluridol, and clopimozide, inhibit [3H]nitrendipine binding with IC50 values of 13-30 nM. This inhibition involves receptors for the verapamil/prenylamine class of calcium channel antagonists. These diph...
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.80.16.5122
更新日期:1983-08-01 00:00:00
abstract::Periodicities in the polar/apolar character of the amino acid sequence of a protein can be examined by assigning to each residue a numerical hydrophobicity and searching for periodicity in the resulting one-dimensional function. The strength of each periodic component is the quantity that has been termed the hydrophob...
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.81.1.140
更新日期:1984-01-01 00:00:00
abstract::In this paper is presented the theory of a class of locally convex lattices (L-lattices) of real functions which generalize the classical Lebesgue spaces. The monotone and dominated convergence theorems for convergence almost everywhere and sequential and order completeness of such lattices are established. These resu...
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.66.2.275
更新日期:1970-06-01 00:00:00
abstract::When we grasp and manipulate an object, populations of tactile nerve fibers become activated and convey information about the shape, size, and texture of the object and its motion across the skin. The response properties of tactile fibers have been extensively characterized in single-unit recordings, yielding importan...
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.1704856114
更新日期:2017-07-11 00:00:00
abstract::Wild-type newborn mice are characterized by the ability of certain liver-specific genes encoding various enzymes and mapping on different chromosomes to respond to glucocorticoid induction. Newborn mice homozygous for deletions at and around the albino locus on chromosome 7 fail to develop this competence for hormone-...
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.88.13.5607
更新日期:1991-07-01 00:00:00
abstract::HUMAN LIVER ALCOHOL DEHYDROGENASE (ALCOHOL: NAD(+) oxidoreductase, EC 1.1.1.1), homogeneous by physicochemical criteria, has been available in quantity only recently [Lange, L. G. & Vallee, B. L. (1976) Biochemistry 15, 4681-4686]. Until now, the biochemical basis of human alcohol metabolism had to be extrapolated fro...
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.74.10.4378
更新日期:1977-10-01 00:00:00
abstract::Genetic evidence indicates that the PrlA (SecY) protein of Escherichia coli functions as a membrane integrated signal sequence receptor in protein "export"--i.e., in protein translocation across (or integration into) the plasma membrane. We have raised antibodies in rabbits against two synthetic peptides representing ...
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.86.6.1895
更新日期:1989-03-01 00:00:00