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  • 2003  (81)
  • 1
    Publication Date: 2003-04-12
    Description: DNA sequence and annotation of the entire human chromosome 7, encompassing nearly 158 million nucleotides of DNA and 1917 gene structures, are presented. To generate a higher order description, additional structural features such as imprinted genes, fragile sites, and segmental duplications were integrated at the level of the DNA sequence with medical genetic data, including 440 chromosome rearrangement breakpoints associated with disease. This approach enabled the discovery of candidate genes for developmental diseases including autism.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2882961/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2882961/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Scherer, Stephen W -- Cheung, Joseph -- MacDonald, Jeffrey R -- Osborne, Lucy R -- Nakabayashi, Kazuhiko -- Herbrick, Jo-Anne -- Carson, Andrew R -- Parker-Katiraee, Layla -- Skaug, Jennifer -- Khaja, Razi -- Zhang, Junjun -- Hudek, Alexander K -- Li, Martin -- Haddad, May -- Duggan, Gavin E -- Fernandez, Bridget A -- Kanematsu, Emiko -- Gentles, Simone -- Christopoulos, Constantine C -- Choufani, Sanaa -- Kwasnicka, Dorota -- Zheng, Xiangqun H -- Lai, Zhongwu -- Nusskern, Deborah -- Zhang, Qing -- Gu, Zhiping -- Lu, Fu -- Zeesman, Susan -- Nowaczyk, Malgorzata J -- Teshima, Ikuko -- Chitayat, David -- Shuman, Cheryl -- Weksberg, Rosanna -- Zackai, Elaine H -- Grebe, Theresa A -- Cox, Sarah R -- Kirkpatrick, Susan J -- Rahman, Nazneen -- Friedman, Jan M -- Heng, Henry H Q -- Pelicci, Pier Giuseppe -- Lo-Coco, Francesco -- Belloni, Elena -- Shaffer, Lisa G -- Pober, Barbara -- Morton, Cynthia C -- Gusella, James F -- Bruns, Gail A P -- Korf, Bruce R -- Quade, Bradley J -- Ligon, Azra H -- Ferguson, Heather -- Higgins, Anne W -- Leach, Natalia T -- Herrick, Steven R -- Lemyre, Emmanuelle -- Farra, Chantal G -- Kim, Hyung-Goo -- Summers, Anne M -- Gripp, Karen W -- Roberts, Wendy -- Szatmari, Peter -- Winsor, Elizabeth J T -- Grzeschik, Karl-Heinz -- Teebi, Ahmed -- Minassian, Berge A -- Kere, Juha -- Armengol, Lluis -- Pujana, Miguel Angel -- Estivill, Xavier -- Wilson, Michael D -- Koop, Ben F -- Tosi, Sabrina -- Moore, Gudrun E -- Boright, Andrew P -- Zlotorynski, Eitan -- Kerem, Batsheva -- Kroisel, Peter M -- Petek, Erwin -- Oscier, David G -- Mould, Sarah J -- Dohner, Hartmut -- Dohner, Konstanze -- Rommens, Johanna M -- Vincent, John B -- Venter, J Craig -- Li, Peter W -- Mural, Richard J -- Adams, Mark D -- Tsui, Lap-Chee -- 38103/Canadian Institutes of Health Research/Canada -- P01 GM061354/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2003 May 2;300(5620):767-72. Epub 2003 Apr 10.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Genetics and Genomic Biology, The Hospital for Sick Children, Toronto, Ontario, Canada, M5G 1X8. steve@genet.sickkids.on.ca〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12690205" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Autistic Disorder/genetics ; Chromosome Aberrations ; Chromosome Fragile Sites ; Chromosome Fragility ; Chromosome Mapping ; Chromosomes, Human, Pair 7/*genetics ; Computational Biology ; Congenital Abnormalities/genetics ; CpG Islands ; DNA, Complementary ; Databases, Genetic ; Euchromatin/genetics ; Expressed Sequence Tags ; Gene Duplication ; Genes, Overlapping ; Genetic Diseases, Inborn/genetics ; Genomic Imprinting ; Humans ; In Situ Hybridization, Fluorescence ; Limb Deformities, Congenital/genetics ; Mice ; Molecular Sequence Data ; Mutation ; Neoplasms/genetics ; Pseudogenes ; RNA/genetics ; Retroelements ; *Sequence Analysis, DNA ; Williams Syndrome/genetics
    Print ISSN: 0036-8075
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  • 2
    Publication Date: 2003-07-19
    Description: Glucokinase (GK) plays a key role in whole-body glucose homeostasis by catalyzing the phosphorylation of glucose in cells that express this enzyme, such as pancreatic beta cells and hepatocytes. We describe a class of antidiabetic agents that act as nonessential, mixed-type GK activators (GKAs) that increase the glucose affinity and maximum velocity (Vmax) of GK. GKAs augment both hepatic glucose metabolism and glucose-induced insulin secretion from isolated rodent pancreatic islets, consistent with the expression and function of GK in both cell types. In several rodent models of type 2 diabetes mellitus, GKAs lowered blood glucose levels, improved the results of glucose tolerance tests, and increased hepatic glucose uptake. These findings may lead to the development of new drug therapies for diabetes.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Grimsby, Joseph -- Sarabu, Ramakanth -- Corbett, Wendy L -- Haynes, Nancy-Ellen -- Bizzarro, Fred T -- Coffey, John W -- Guertin, Kevin R -- Hilliard, Darryl W -- Kester, Robert F -- Mahaney, Paige E -- Marcus, Linda -- Qi, Lida -- Spence, Cheryl L -- Tengi, John -- Magnuson, Mark A -- Chu, Chang An -- Dvorozniak, Mark T -- Matschinsky, Franz M -- Grippo, Joseph F -- New York, N.Y. -- Science. 2003 Jul 18;301(5631):370-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Metabolic Diseases, Hoffmann-La Roche Inc., Nutley, NJ 07110, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12869762" target="_blank"〉PubMed〈/a〉
    Keywords: Adaptor Proteins, Signal Transducing ; Allosteric Regulation ; Animals ; Blood Glucose/metabolism ; *Carrier Proteins ; Diabetes Mellitus, Type 2/*drug therapy/metabolism ; Dose-Response Relationship, Drug ; Drug Evaluation, Preclinical ; Enzyme Activation ; Enzyme Activators/chemistry/pharmacology ; Glucokinase/*metabolism ; Glucose/*metabolism ; Glucose Tolerance Test ; Homeostasis ; Humans ; Hypoglycemic Agents/chemistry/pharmacology ; Insulin/blood/*secretion ; Islets of Langerhans/*drug effects/secretion ; Keto Acids/metabolism ; Liver/*drug effects/metabolism ; Liver Glycogen/biosynthesis ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Obese ; Proteins/metabolism/pharmacology ; Rats ; Rats, Wistar ; Recombinant Proteins/metabolism ; Stereoisomerism ; Thiazoles/chemistry/*pharmacology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 3
    Publication Date: 2003-08-09
    Description: Hybridization is frequent in many organismal groups, but its role in adaptation is poorly understood. In sunflowers, species found in the most extreme habitats are ancient hybrids, and new gene combinations generated by hybridization are speculated to have contributed to ecological divergence. This possibility was tested through phenotypic and genomic comparisons of ancient and synthetic hybrids. Most trait differences in ancient hybrids could be recreated by complementary gene action in synthetic hybrids and were favored by selection. The same combinations of parental chromosomal segments required to generate extreme phenotypes in synthetic hybrids also occurred in ancient hybrids. Thus, hybridization facilitated ecological divergence in sunflowers.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rieseberg, Loren H -- Raymond, Olivier -- Rosenthal, David M -- Lai, Zhao -- Livingstone, Kevin -- Nakazato, Takuya -- Durphy, Jennifer L -- Schwarzbach, Andrea E -- Donovan, Lisa A -- Lexer, Christian -- R01 G59065/PHS HHS/ -- New York, N.Y. -- Science. 2003 Aug 29;301(5637):1211-6. Epub 2003 Aug 7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biology, Indiana University, Bloomington, IN 47405, USA. lriesebe@indiana.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12907807" target="_blank"〉PubMed〈/a〉
    Keywords: *Adaptation, Physiological ; *Biological Evolution ; Chromosome Mapping ; Diploidy ; *Ecosystem ; Environment ; Genes, Plant ; Genome, Plant ; Genotype ; Helianthus/*genetics/physiology ; *Hybridization, Genetic ; Microsatellite Repeats ; Mutation ; Phenotype ; Quantitative Trait Loci ; Selection, Genetic ; Species Specificity ; United States
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 4
    Publication Date: 2003-11-25
    Description: Calcium ion (Ca2+) influx through voltage-gated Ca2+ channels is important for the regulation of vascular tone. Activation of L-type Ca2+ channels initiates muscle contraction; however, the role of T-type Ca2+ channels (T-channels) is not clear. We show that mice deficient in the alpha1H T-type Ca2+ channel (alpha(1)3.2-null) have constitutively constricted coronary arterioles and focal myocardial fibrosis. Coronary arteries isolated from alpha(1)3.2-null arteries showed normal contractile responses, but reduced relaxation in response to acetylcholine and nitroprusside. Furthermore, acute blockade of T-channels with Ni2+ prevented relaxation of wild-type coronary arteries. Thus, Ca2+ influx through alpha1H T-type Ca2+ channels is essential for normal relaxation of coronary arteries.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chen, Chien-Chang -- Lamping, Kathryn G -- Nuno, Daniel W -- Barresi, Rita -- Prouty, Sally J -- Lavoie, Julie L -- Cribbs, Leanne L -- England, Sarah K -- Sigmund, Curt D -- Weiss, Robert M -- Williamson, Roger A -- Hill, Joseph A -- Campbell, Kevin P -- New York, N.Y. -- Science. 2003 Nov 21;302(5649):1416-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, University of Iowa, Iowa City, IA 52242, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/14631046" target="_blank"〉PubMed〈/a〉
    Keywords: Acetylcholine/pharmacology ; Animals ; Arteries/drug effects/*physiology ; Calcium/*metabolism ; Calcium Channels, T-Type/genetics/*physiology ; Coronary Vessels/drug effects/pathology/*physiology ; Echocardiography ; Electrocardiography ; Endothelium, Vascular/drug effects/physiology ; Female ; Fibrosis ; Ganglia, Spinal/cytology ; Gene Targeting ; Heart/physiology ; Heart Rate ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Muscle, Smooth, Vascular/physiology ; Myocardium/pathology ; Neurons/metabolism ; Nickel/pharmacology ; Nitric Oxide/physiology ; Nitric Oxide Donors/pharmacology ; Nitroprusside/pharmacology ; Patch-Clamp Techniques ; Vasoconstriction/drug effects ; *Vasodilation/drug effects
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 5
    Publication Date: 2003-08-02
    Description: Over 225,000 independent Agrobacterium transferred DNA (T-DNA) insertion events in the genome of the reference plant Arabidopsis thaliana have been created that represent near saturation of the gene space. The precise locations were determined for more than 88,000 T-DNA insertions, which resulted in the identification of mutations in more than 21,700 of the approximately 29,454 predicted Arabidopsis genes. Genome-wide analysis of the distribution of integration events revealed the existence of a large integration site bias at both the chromosome and gene levels. Insertion mutations were identified in genes that are regulated in response to the plant hormone ethylene.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Alonso, Jose M -- Stepanova, Anna N -- Leisse, Thomas J -- Kim, Christopher J -- Chen, Huaming -- Shinn, Paul -- Stevenson, Denise K -- Zimmerman, Justin -- Barajas, Pascual -- Cheuk, Rosa -- Gadrinab, Carmelita -- Heller, Collen -- Jeske, Albert -- Koesema, Eric -- Meyers, Cristina C -- Parker, Holly -- Prednis, Lance -- Ansari, Yasser -- Choy, Nathan -- Deen, Hashim -- Geralt, Michael -- Hazari, Nisha -- Hom, Emily -- Karnes, Meagan -- Mulholland, Celene -- Ndubaku, Ral -- Schmidt, Ian -- Guzman, Plinio -- Aguilar-Henonin, Laura -- Schmid, Markus -- Weigel, Detlef -- Carter, David E -- Marchand, Trudy -- Risseeuw, Eddy -- Brogden, Debra -- Zeko, Albana -- Crosby, William L -- Berry, Charles C -- Ecker, Joseph R -- New York, N.Y. -- Science. 2003 Aug 1;301(5633):653-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Genomic Analysis Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12893945" target="_blank"〉PubMed〈/a〉
    Keywords: 3' Untranslated Regions ; 5' Untranslated Regions ; Alleles ; Arabidopsis/*genetics/metabolism ; Arabidopsis Proteins/genetics/metabolism ; Base Composition ; Chromosomes, Plant/genetics ; DNA, Bacterial/genetics ; DNA, Plant/chemistry/genetics ; Ethylenes/pharmacology ; Exons ; Expressed Sequence Tags ; Gene Expression ; Gene Expression Profiling ; Gene Expression Regulation, Plant/drug effects ; Genes, Plant ; *Genome, Plant ; Introns ; *Mutagenesis, Insertional ; Mutation ; Oligonucleotide Array Sequence Analysis ; Promoter Regions, Genetic ; Recombination, Genetic ; Rhizobium/genetics
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  • 6
    Publication Date: 2003-10-18
    Description: The Rac1 guanosine triphosphatase (GTPase) has been implicated in multiple cellular functions, including actin dynamics, proliferation, apoptosis, adhesion, and migration resulting from signaling by multiple receptors, including the B cell antigen receptor (BCR). We used conditional gene targeting to generate mice with specific Rac1 deficiency in the B cell lineage. In the absence of both Rac1 and the highly related Rac2, B cell development was almost completely blocked. Both GTPases were required to transduce BCR signals leading to proliferation, survival and up-regulation of BAFF-R, a receptor for BAFF, a key survival molecule required for B cell development and maintenance.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Walmsley, Marita J -- Ooi, Steen K T -- Reynolds, Lucinda F -- Smith, Susan Harless -- Ruf, Sandra -- Mathiot, Anne -- Vanes, Lesley -- Williams, David A -- Cancro, Michael P -- Tybulewicz, Victor L J -- R01 AI042990/AI/NIAID NIH HHS/ -- R01 AI054488/AI/NIAID NIH HHS/ -- R01 DK62757/DK/NIDDK NIH HHS/ -- T32 CA009140/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2003 Oct 17;302(5644):459-62.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Immune Cell Biology, National Institute for Medical Research, The Ridgeway, Mill Hill, London, NW7 1AA, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/14564011" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; B-Cell Activating Factor ; B-Cell Activation Factor Receptor ; B-Lymphocyte Subsets/physiology ; B-Lymphocytes/*physiology ; Cell Differentiation ; Cell Division ; Cell Lineage ; Cell Survival ; Female ; Gene Targeting ; Lymphocyte Activation ; Male ; Membrane Proteins/metabolism ; Mice ; Mice, Inbred C57BL ; Receptors, Antigen, B-Cell/*metabolism ; Receptors, Tumor Necrosis Factor/genetics/metabolism ; Recombination, Genetic ; *Signal Transduction ; Spleen/cytology ; Tumor Necrosis Factor-alpha/metabolism ; Up-Regulation ; rac GTP-Binding Proteins/*physiology ; rac1 GTP-Binding Protein/*physiology
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 7
    Publication Date: 2003-02-08
    Description: We report the design and total chemical synthesis of "synthetic erythropoiesis protein" (SEP), a 51-kilodalton protein-polymer construct consisting of a 166-amino-acid polypeptide chain and two covalently attached, branched, and monodisperse polymer moieties that are negatively charged. The ability to control the chemistry allowed us to synthesize a macromolecule of precisely defined covalent structure. SEP was homogeneous as shown by high-resolution analytical techniques, with a mass of 50,825 +/-10 daltons by electrospray mass spectrometry, and with a pI of 5.0. In cell and animal assays for erythropoiesis, SEP displayed potent biological activity and had significantly prolonged duration of action in vivo. These chemical methods are a powerful tool in the rational design of protein constructs with potential therapeutic applications.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kochendoerfer, Gerd G -- Chen, Shiah-Yun -- Mao, Feng -- Cressman, Sonya -- Traviglia, Stacey -- Shao, Haiyan -- Hunter, Christie L -- Low, Donald W -- Cagle, E Neil -- Carnevali, Maia -- Gueriguian, Vincent -- Keogh, Peter J -- Porter, Heather -- Stratton, Stephen M -- Wiedeke, M Con -- Wilken, Jill -- Tang, Jie -- Levy, Jay J -- Miranda, Les P -- Crnogorac, Milan M -- Kalbag, Suresh -- Botti, Paolo -- Schindler-Horvat, Janice -- Savatski, Laura -- Adamson, John W -- Kung, Ada -- Kent, Stephen B H -- Bradburne, James A -- New York, N.Y. -- Science. 2003 Feb 7;299(5608):884-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Gryphon Therapeutics, 250 East Grand Avenue, Suite 90, South San Francisco, CA 94080, USA. Gkochendoerfer@gryphonRX.com〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12574628" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Cell Line ; Circular Dichroism ; *Drug Design ; Drug Stability ; Electrophoresis, Polyacrylamide Gel ; *Erythropoiesis ; Erythropoietin/chemistry/pharmacology ; Hematocrit ; Humans ; Isoelectric Point ; Mice ; Molecular Sequence Data ; Molecular Structure ; Molecular Weight ; *Polymers/*chemical synthesis/*chemistry/pharmacokinetics/pharmacology ; Protein Folding ; Proteins/*chemical synthesis/*chemistry/pharmacokinetics/pharmacology ; Rats ; Receptors, Erythropoietin/drug effects/metabolism ; Recombinant Proteins ; Spectrometry, Mass, Electrospray Ionization
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  • 8
    Publication Date: 2003-05-31
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Woods, Gordon L -- White, Kenneth L -- Vanderwall, Dirk K -- Li, Guang-Peng -- Aston, Kenneth I -- Bunch, Thomas D -- Meerdo, Lora N -- Pate, Barry J -- New York, N.Y. -- Science. 2003 Aug 22;301(5636):1063. Epub 2003 May 29.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Northwest Equine Reproduction Laboratory, Department of Animal and Veterinary Science, University of Idaho, Moscow, ID 83844, USA. gwoods@uidaho.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12775846" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Calcium/metabolism ; Cell Line ; *Cloning, Organism ; Embryo Transfer ; Embryo, Mammalian ; Embryonic and Fetal Development ; Equidae/*embryology/*genetics ; Female ; Fibroblasts ; Horses ; Male ; *Nuclear Transfer Techniques ; Oocytes/metabolism ; Pregnancy
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 9
    Publication Date: 2003-09-27
    Description: A survey of the dog genome sequence (6.22 million sequence reads; 1.5x coverage) demonstrates the power of sample sequencing for comparative analysis of mammalian genomes and the generation of species-specific resources. More than 650 million base pairs (〉25%) of dog sequence align uniquely to the human genome, including fragments of putative orthologs for 18,473 of 24,567 annotated human genes. Mutation rates, conserved synteny, repeat content, and phylogeny can be compared among human, mouse, and dog. A variety of polymorphic elements are identified that will be valuable for mapping the genetic basis of diseases and traits in the dog.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kirkness, Ewen F -- Bafna, Vineet -- Halpern, Aaron L -- Levy, Samuel -- Remington, Karin -- Rusch, Douglas B -- Delcher, Arthur L -- Pop, Mihai -- Wang, Wei -- Fraser, Claire M -- Venter, J Craig -- New York, N.Y. -- Science. 2003 Sep 26;301(5641):1898-903.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉The Institute for Genomic Research, Rockville, MD 20850, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/14512627" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Chromosomes, Mammalian/genetics ; Computational Biology ; Conserved Sequence ; Contig Mapping ; DNA, Intergenic ; Dogs/*genetics ; Genetic Variation ; *Genome ; Genome, Human ; Genomics ; Humans ; Long Interspersed Nucleotide Elements ; Male ; Mice/genetics ; Molecular Sequence Data ; Mutation ; Phylogeny ; Physical Chromosome Mapping ; Polymorphism, Single Nucleotide ; RNA, Messenger/genetics ; Repetitive Sequences, Nucleic Acid ; Sequence Alignment ; *Sequence Analysis, DNA ; Short Interspersed Nucleotide Elements ; Synteny
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  • 10
    Publication Date: 2003-09-06
    Description: Wnt proteins, regulators of development in many organisms, bind to seven transmembrane-spanning (7TMS) receptors called frizzleds, thereby recruiting the cytoplasmic molecule dishevelled (Dvl) to the plasma membrane.Frizzled-mediated endocytosis of Wg (a Drosophila Wnt protein) and lysosomal degradation may regulate the formation of morphogen gradients. Endocytosis of Frizzled 4 (Fz4) in human embryonic kidney 293 cells was dependent on added Wnt5A protein and was accomplished by the multifunctional adaptor protein beta-arrestin 2 (betaarr2), which was recruited to Fz4 by binding to phosphorylated Dvl2. These findings provide a previously unrecognized mechanism for receptor recruitment of beta-arrestin and demonstrate that Dvl plays an important role in the endocytosis of frizzled, as well as in promoting signaling.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chen, Wei -- ten Berge, Derk -- Brown, Jeff -- Ahn, Seungkirl -- Hu, Liaoyuan A -- Miller, William E -- Caron, Marc G -- Barak, Larry S -- Nusse, Roel -- Lefkowitz, Robert J -- HL 16037/HL/NHLBI NIH HHS/ -- HL 61365/HL/NHLBI NIH HHS/ -- NS 19576/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 2003 Sep 5;301(5638):1391-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Departments of Medicine and Biochemistry, Duke University Medical Center, Durham, NC 27710, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12958364" target="_blank"〉PubMed〈/a〉
    Keywords: Adaptor Proteins, Signal Transducing ; Animals ; Arrestins/genetics/*metabolism ; Cell Line ; Cell Membrane/metabolism ; Clathrin/metabolism ; Cytoplasm/metabolism ; *Endocytosis ; Frizzled Receptors ; Humans ; Mice ; Phosphoproteins/metabolism ; Phosphorylation ; Protein Kinase C/antagonists & inhibitors/metabolism ; Proteins/genetics/*metabolism ; Proto-Oncogene Proteins/*metabolism/pharmacology ; RNA, Small Interfering ; Recombinant Fusion Proteins/metabolism ; Signal Transduction ; Wnt Proteins
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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