Abstract:
:We report that oxytocin (Oxt) receptors (Oxtrs), on stimulation by the ligand Oxt, translocate into the nucleus of osteoblasts, implicating this process in the action of Oxt on osteoblast maturation. Sequential immunocytochemistry of intact cells or isolated nucleoplasts stripped of the outer nuclear membrane showed progressive nuclear localization of the Oxtr; this nuclear translocation was confirmed by monitoring the movement of Oxtr-EGFP as well as by immunogold labeling. Nuclear Oxtr localization was conclusively shown by Western immunoblotting and MS of nuclear lysate proteins. We found that the passage of Oxtrs into the nucleus was facilitated by successive interactions with β-arrestins (Arrbs), the small GTPase Rab5, importin-β (Kpnb1), and transportin-1 (Tnpo1). siRNA-mediated knockdown of Arrb1, Arrb2, or Tnpo1 abrogated Oxt-induced expression of the osteoblast differentiation genes osterix (Sp7), Atf4, bone sialoprotein (Ibsp), and osteocalcin (Bglap) without affecting Erk phosphorylation. Likewise and again, without affecting pErk, inhibiting Arrb recruitment by mutating Ser rich clusters of the nuclear localization signal to Ala abolished nuclear import and Oxtr-induced gene expression. These studies define a previously unidentified mechanism for Oxtr action on bone and open possibilities for direct transcriptional modulation by nuclear G protein-coupled receptors.
journal_name
Proc Natl Acad Sci U S Aauthors
Di Benedetto A,Sun L,Zambonin CG,Tamma R,Nico B,Calvano CD,Colaianni G,Ji Y,Mori G,Grano M,Lu P,Colucci S,Yuen T,New MI,Zallone A,Zaidi Mdoi
10.1073/pnas.1419349111subject
Has Abstractpub_date
2014-11-18 00:00:00pages
16502-7issue
46eissn
0027-8424issn
1091-6490pii
1419349111journal_volume
111pub_type
杂志文章abstract::NK cells are promising effectors for tumor adoptive immunotherapy, particularly when considering the targeting of MHC class I low or negative tumors. Yet, NK cells cannot respond to many tumors, which is particularly the case for nonhematopoietic tumors such as carcinomas or melanoma even when these cells lose MHC cla...
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.0804788105
更新日期:2008-11-11 00:00:00
abstract::The importance of carbon in Earth's mantle greatly exceeds its modest abundance of approximately 1,000-4,000 ppm. Carbon is a constituent of key terrestrial volatiles (CO, CO(2), CH(4)), it forms diamonds, and it may also contribute to the bulk electrical properties of the silicate Earth. In contrast to that of the 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.0710806105
更新日期:2008-06-24 00:00:00
abstract::Long-range conformational changes in proteins are ubiquitous in biology for the transmission and amplification of signals; such conformational changes can be triggered by small-amplitude, nanosecond protein domain motion. Understanding how conformational changes are initiated requires the characterization of protein d...
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.0503388102
更新日期:2005-12-06 00:00:00
abstract::Bilateria are currently subdivided into three superclades: Deuterostomia, Ecdysozoa, and Lophotrochozoa. Within this new taxonomic frame, acoelomate Platyhelminthes, for a long time held to be basal bilaterians, are now considered spiralian lophotrochozoans. However, recent 18S rDNA [small subunit (SSU)] analyses have...
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.172390199
更新日期:2002-08-20 00:00:00
abstract::Sonic hedgehog (Shh) plays an integral role in both the anterior-posterior (A-P) patterning and expansion of developing vertebrate limbs through a feedback loop involving Fgfs, Bmps, and Gremlin. In bat limbs A-P patterning and the size of the digital field are unique. The posterior digits of the forelimb are elongate...
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.0805308105
更新日期:2008-11-04 00:00:00
abstract::Nucleosomes in eukaryotes act as platforms for the dynamic integration of epigenetic information. Posttranslational modifications are reversibly added or removed and core histones exchanged for paralogous variants, in concert with changing demands on transcription and genome accessibility. Histones are also common 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.2007056117
更新日期:2020-12-29 00:00:00
abstract::Wild bees are highly valuable pollinators. Along with managed honey bees, they provide a critical ecosystem service by ensuring stable pollination to agriculture and wild plant communities. Increasing concern about the welfare of both wild and managed pollinators, however, has prompted recent calls for national evalua...
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.1517685113
更新日期:2016-01-05 00:00:00
abstract::Fluorescence photobleaching recovery was used to measure the lateral diffusion coefficient and mobile fraction of surface immunoglobulin (sIg), Thy-1 antigen, and a lipid probe in the plasma membrane of mouse lymphocytes. The lipid probe (3,3'-dioctadecylindocarbocyanine) had a mean (+/-SD) diffusion coefficient of (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.76.10.5163
更新日期:1979-10-01 00:00:00
abstract::Protecting hydrologic connectivity of freshwater ecosystems is fundamental to ensuring species persistence, ecosystem integrity, and human well-being. More frequent and severe droughts associated with climate change are poised to significantly alter flow intermittence patterns and hydrologic connectivity in dryland 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.1320890111
更新日期:2014-09-23 00:00:00
abstract::Protein-binding DNA sequence elements encode a variety of regulated functions of genomes. Information about such elements is currently in a state of rapid growth, but improved methods are required to characterize the sequence specificity of DNA-binding proteins. We have established an in vitro method for specific and ...
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.0611229104
更新日期:2007-02-27 00:00:00
abstract::The mammalian RNase A superfamily comprises a diverse array of ribonucleolytic proteins that have a variety of biochemical activities and physiological functions. Two rapidly evolving RNases of higher primates are of particular interest as they are major secretory proteins of eosinophilic leukocytes and have been foun...
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.080071397
更新日期:2000-04-25 00:00:00
abstract::The regional chromosomal location of the human gene for plasminogen activator inhibitor type 1 (PAI1) was determined by three independent methods of gene mapping. PAI1 was localized first to 7cen-q32 and then to 7q21.3-q22 by Southern blot hybridization analysis of a panel of human and mouse somatic cell hybrids with ...
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.84.23.8548
更新日期:1987-12-01 00:00:00
abstract::We have examined the functional consequences of mutations present in defective alleles of the retinoblastoma susceptibility gene (RB1) isolated from two spontaneously arising tumors. Unlike cDNA clones expressing the wild-type protein p110Rb, those encoding the two mutant proteins failed to induce the appearance of se...
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.88.8.3033
更新日期:1991-04-15 00:00:00
abstract::Matrix metalloprotease type 9 (MMP-9) has been functionally implicated in VEGF activation, the induction and maintenance of chronic angiogenesis, and early stage tumor growth in a number of mouse models of cancer. In this article, we have identified two inflammatory cell types that are major sources of MMP-9 in the 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.0601807103
更新日期:2006-08-15 00:00:00
abstract::Although neural circuits mediating various simple behaviors have been delineated, those generating more complex behaviors are less well described. The discrete structure of avian song control nuclei promises that circuits controlling complex behaviors, such as birdsong, can also be understood. To this end, we develope...
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.88.10.4075
更新日期:1991-05-15 00:00:00
abstract::The Sleeping Beauty (SB) transposon system can integrate foreign sequences of DNA in the genome of mouse somatic cells eliciting long-term expression in vivo. This technology holds great promise for human gene therapy as a nonviral technology to deliver therapeutic genes. SB also provides a means to study the effects ...
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.0502974102
更新日期:2005-11-22 00:00:00
abstract::Although rigorous measures of similarity for sequence and structure are now well established, the problem of defining functional relationships has been particularly daunting. Here, we present several manifold embedding techniques to compute distances between Gene Ontology (GO) functional annotations and consequently e...
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.0702965104
更新日期:2007-07-03 00:00:00
abstract::Gene expression in higher organisms is thought to be regulated by a complex network of transcription factor binding and chromatin modifications, yet the relative importance of these two factors remains a matter of debate. Here, we show that a computational approach allows surprisingly accurate prediction of histone mo...
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.1412081111
更新日期:2014-09-16 00:00:00
abstract::We demonstrate theoretically and experimentally the spontaneous clustering of solitons in partially coherent wavefronts during the final stages of pattern formation initiated by modulation instability and noise. ...
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.072287299
更新日期:2002-04-16 00:00:00
abstract::Wnt signaling regulates many aspects of development by increasing the signaling activity of beta-catenin. Axin is a negative regulator of the Wnt signaling pathway, and it is responsible for the formation of the beta-catenin degradation complex. Genetic studies with Drosophila suggest that Axin promotes cytoplasmic lo...
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.0307344101
更新日期:2004-03-02 00:00:00
abstract::We describe a procedure for predicting the tertiary folds of alpha-helical proteins from their primary sequences. The central component of the procedure is a method for predicting interhelical contacts that is based on a helix-packing model. Instead of predicting the individual contacts, our method attempts to identif...
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.052003799
更新日期:2002-03-19 00:00:00
abstract::Nutrition recommendations worldwide emphasize ingestion of plant-based diets rather than diets that rely primarily on animal products. However, this plant-based diet could limit the intake of essential nutrients such as calcium. Osteoporosis is one of the world's most prevalent nutritional disorders, and inadequate di...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章,随机对照试验
doi:10.1073/pnas.0709005105
更新日期:2008-02-05 00:00:00
abstract::We have utilized a recombinant vector system designed to study gene control elements by fusing them to the Escherichia coli galactokinase gene (galK) to examine the effects of gene expression that result from introducing changes into the 5' noncoding leader region of the galK transcription unit. We varied the length o...
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.81.24.7698
更新日期:1984-12-01 00:00:00
abstract::Maintaining the fidelity of nascent peptide chain (NP) synthesis is essential for proteome integrity and cellular health. Ribosome-associated quality control (RQC) serves to resolve stalled translation, during which untemplated Ala/Thr residues are added C terminally to stalled peptide, as shown during C-terminal Ala ...
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.2005506117
更新日期:2020-10-06 00:00:00
abstract::Phytochrome A (phyA) is the only plant photoreceptor that perceives far-red light and then mediates various responses to this signal. Phosphorylation and dephosphorylation of oat phyA have been extensively studied, and it was shown that phosphorylation of a serine residue in the hinge region of oat phyA could regulate...
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.1813162115
更新日期:2018-12-11 00:00:00
abstract::The mammalian gastrointestinal tract harbors thousands of bacterial species that include symbionts as well as potential pathogens. The immune responses that limit access of these bacteria to underlying tissue remain poorly defined. Here we show that γδ intraepithelial lymphocytes (γδ IEL) of the small intestine produc...
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.1019574108
更新日期:2011-05-24 00:00:00
abstract::Real-world studies show that the facial expressions produced during pain and orgasm-two different and intense affective experiences-are virtually indistinguishable. However, this finding is counterintuitive, because facial expressions are widely considered to be a powerful tool for social interaction. Consequently, de...
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.1807862115
更新日期:2018-10-23 00:00:00
abstract::The ability to control drops and their movements on phobic surfaces is important in printing or patterning, microfluidic devices, and water-repellent materials. These materials are always micro-/nanotextured, and a natural limitation of repellency occurs when drops are small enough (as in a dew) to get trapped in the ...
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.1506874112
更新日期:2015-07-28 00:00:00
abstract::The ability to respond selectively to particular frequency components of sensory inputs is fundamental to signal processing in the ear. The frog (Rana pipiens) sacculus, which is used for social communication and escape behaviors, is an exquisitely sensitive detector of sounds and ground-borne vibrations in the 5- to ...
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.0511005103
更新日期:2006-02-21 00:00:00
abstract::Unit electrical activity was recorded from single neurons in the isolated lumbo-sacral spinal cord of 14- to 19-day chick embryos, in situ. Spinal cord transection was combined with transection of all lumbo-sacral dorsal roots. The spontaneous discharge of cells is confined, for the most part, to the lower two thirds ...
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.66.1.40
更新日期:1970-05-01 00:00:00