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  • American Association for the Advancement of Science (AAAS)  (8)
  • 2005-2009  (8)
  • 1
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    Interpreting sequences from mastodon and T. rex (2007)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2007-09-08
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Asara, John M -- Garavelli, John S -- Slatter, David A -- Schweitzer, Mary H -- Freimark, Lisa M -- Phillips, Matthew -- Cantley, Lewis C -- New York, N.Y. -- Science. 2007 Sep 7;317(5843):1324-5.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17823333" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Bone and Bones/chemistry ; Collagen/*chemistry ; *Dinosaurs ; *Elephants ; *Fossils ; Glycine/chemistry ; Mass Spectrometry ; Molecular Sequence Data ; Proline/chemistry ; Tandem Mass Spectrometry
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 2
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    Protein sequences from mastodon and Tyrannosaurus rex revealed by mass spectrometry (2007)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2007-04-14
    Description: Fossilized bones from extinct taxa harbor the potential for obtaining protein or DNA sequences that could reveal evolutionary links to extant species. We used mass spectrometry to obtain protein sequences from bones of a 160,000- to 600,000-year-old extinct mastodon (Mammut americanum) and a 68-million-year-old dinosaur (Tyrannosaurus rex). The presence of T. rex sequences indicates that their peptide bonds were remarkably stable. Mass spectrometry can thus be used to determine unique sequences from ancient organisms from peptide fragmentation patterns, a valuable tool to study the evolution and adaptation of ancient taxa from which genomic sequences are unlikely to be obtained.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Asara, John M -- Schweitzer, Mary H -- Freimark, Lisa M -- Phillips, Matthew -- Cantley, Lewis C -- New York, N.Y. -- Science. 2007 Apr 13;316(5822):280-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Signal Transduction, Beth Israel Deaconess Medical Center, Boston, MA 02115, USA. jasara@bidmc.harvard.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17431180" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Bone and Bones/*chemistry ; Collagen/chemistry ; *Dinosaurs ; *Elephants ; Evolution, Molecular ; *Fossils ; Humans ; *Mass Spectrometry ; Molecular Sequence Data ; Proteins/analysis/*chemistry ; Reptilian Proteins/analysis/*chemistry ; Sequence Alignment ; Sequence Analysis, Protein ; Struthioniformes
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 3
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    Biomolecular characterization and protein sequences of the Campanian hadrosaur B. canadensis (2009)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2009-05-02
    Description: Molecular preservation in non-avian dinosaurs is controversial. We present multiple lines of evidence that endogenous proteinaceous material is preserved in bone fragments and soft tissues from an 80-million-year-old Campanian hadrosaur, Brachylophosaurus canadensis [Museum of the Rockies (MOR) 2598]. Microstructural and immunological data are consistent with preservation of multiple bone matrix and vessel proteins, and phylogenetic analyses of Brachylophosaurus collagen sequenced by mass spectrometry robustly support the bird-dinosaur clade, consistent with an endogenous source for these collagen peptides. These data complement earlier results from Tyrannosaurus rex (MOR 1125) and confirm that molecular preservation in Cretaceous dinosaurs is not a unique event.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Schweitzer, Mary H -- Zheng, Wenxia -- Organ, Chris L -- Avci, Recep -- Suo, Zhiyong -- Freimark, Lisa M -- Lebleu, Valerie S -- Duncan, Michael B -- Vander Heiden, Matthew G -- Neveu, John M -- Lane, William S -- Cottrell, John S -- Horner, John R -- Cantley, Lewis C -- Kalluri, Raghu -- Asara, John M -- AA 13913/AA/NIAAA NIH HHS/ -- CA 125550/CA/NCI NIH HHS/ -- DK 55001/DK/NIDDK NIH HHS/ -- DK 61866/DK/NIDDK NIH HHS/ -- DK 62987/DK/NIDDK NIH HHS/ -- R01 AA013913/AA/NIAAA NIH HHS/ -- R01 CA125550/CA/NCI NIH HHS/ -- R01 DK055001/DK/NIDDK NIH HHS/ -- R01 DK062987/DK/NIDDK NIH HHS/ -- New York, N.Y. -- Science. 2009 May 1;324(5927):626-31. doi: 10.1126/science.1165069.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉North Carolina State University, Raleigh, NC 27695, USA. schweitzer@ncsu.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19407199" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Birds/classification ; Bone Demineralization Technique ; Bone Matrix/chemistry ; Collagen/analysis/*chemistry/isolation & purification ; *Dinosaurs/classification ; Elastin/analysis ; Femur/blood supply/*chemistry/ultrastructure ; *Fossils ; Hemoglobins/analysis ; Immunologic Techniques ; Laminin/analysis ; Mass Spectrometry ; Microscopy, Electron, Scanning ; Molecular Sequence Data ; Osteocytes/ultrastructure ; Peptide Fragments/chemistry/isolation & purification ; Phylogeny ; Proteins/analysis/*chemistry/isolation & purification ; Sequence Alignment
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 4
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    The kinase LKB1 mediates glucose homeostasis in liver and therapeutic effects of metformin (2005)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2005-11-26
    Description: The Peutz-Jegher syndrome tumor-suppressor gene encodes a protein-threonine kinase, LKB1, which phosphorylates and activates AMPK [adenosine monophosphate (AMP)-activated protein kinase]. The deletion of LKB1 in the liver of adult mice resulted in a nearly complete loss of AMPK activity. Loss of LKB1 function resulted in hyperglycemia with increased gluconeogenic and lipogenic gene expression. In LKB1-deficient livers, TORC2, a transcriptional coactivator of CREB (cAMP response element-binding protein), was dephosphorylated and entered the nucleus, driving the expression of peroxisome proliferator-activated receptor-gamma coactivator 1alpha (PGC-1alpha), which in turn drives gluconeogenesis. Adenoviral small hairpin RNA (shRNA) for TORC2 reduced PGC-1alpha expression and normalized blood glucose levels in mice with deleted liver LKB1, indicating that TORC2 is a critical target of LKB1/AMPK signals in the regulation of gluconeogenesis. Finally, we show that metformin, one of the most widely prescribed type 2 diabetes therapeutics, requires LKB1 in the liver to lower blood glucose levels.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3074427/" 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/PMC3074427/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Shaw, Reuben J -- Lamia, Katja A -- Vasquez, Debbie -- Koo, Seung-Hoi -- Bardeesy, Nabeel -- Depinho, Ronald A -- Montminy, Marc -- Cantley, Lewis C -- CA84313/CA/NCI NIH HHS/ -- GM056203/GM/NIGMS NIH HHS/ -- GM37828/GM/NIGMS NIH HHS/ -- R01 GM056203/GM/NIGMS NIH HHS/ -- R01 GM056203-09/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2005 Dec 9;310(5754):1642-6. Epub 2005 Nov 24.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA. shaw@salk.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/16308421" target="_blank"〉PubMed〈/a〉
    Keywords: AMP-Activated Protein Kinases ; Animals ; Blood Glucose/analysis ; Diabetes Mellitus, Type 2/drug therapy/metabolism ; Enzyme Activation ; Female ; Gene Expression Regulation ; Gluconeogenesis/genetics ; Glucose/*metabolism ; HeLa Cells ; Homeostasis ; Humans ; Hyperglycemia/drug therapy/metabolism ; Hypoglycemic Agents/*pharmacology/therapeutic use ; Lipogenesis/genetics ; Liver/enzymology/*metabolism ; Male ; Metformin/*pharmacology/therapeutic use ; Mice ; Mice, Obese ; Multienzyme Complexes/*metabolism ; Phosphorylation ; Protein-Serine-Threonine Kinases/genetics/*metabolism ; Signal Transduction ; Trans-Activators/genetics/metabolism ; Transcription Factors
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 5
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    Biochemistry. PI3K charges ahead (2007)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2007-07-14
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lee, Jennifer Y -- Engelman, Jeffrey A -- Cantley, Lewis C -- R01 GM041890/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2007 Jul 13;317(5835):206-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Systems Biology, Harvard Medical School and Division of Signal Transduction, Beth Israel Deaconess Medical Center, Boston, MA 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17626872" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antineoplastic Agents/pharmacology/therapeutic use ; Catalytic Domain ; Cell Membrane/enzymology ; Cell Proliferation ; Cell Survival ; Dimerization ; Enzyme Inhibitors/pharmacology/therapeutic use ; Humans ; Mutation ; Neoplasms/drug therapy/*genetics ; Phosphatidylinositol 3-Kinases/antagonists & ; inhibitors/chemistry/*genetics/*metabolism ; Phosphorylation ; Protein Structure, Tertiary ; Protein Subunits ; src Homology Domains
    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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  • 6
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    MET amplification leads to gefitinib resistance in lung cancer by activating ERBB3 signaling (2007)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2007-04-28
    Description: The epidermal growth factor receptor (EGFR) kinase inhibitors gefitinib and erlotinib are effective treatments for lung cancers with EGFR activating mutations, but these tumors invariably develop drug resistance. Here, we describe a gefitinib-sensitive lung cancer cell line that developed resistance to gefitinib as a result of focal amplification of the MET proto-oncogene. inhibition of MET signaling in these cells restored their sensitivity to gefitinib. MET amplification was detected in 4 of 18 (22%) lung cancer specimens that had developed resistance to gefitinib or erlotinib. We find that amplification of MET causes gefitinib resistance by driving ERBB3 (HER3)-dependent activation of PI3K, a pathway thought to be specific to EGFR/ERBB family receptors. Thus, we propose that MET amplification may promote drug resistance in other ERBB-driven cancers as well.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Engelman, Jeffrey A -- Zejnullahu, Kreshnik -- Mitsudomi, Tetsuya -- Song, Youngchul -- Hyland, Courtney -- Park, Joon Oh -- Lindeman, Neal -- Gale, Christopher-Michael -- Zhao, Xiaojun -- Christensen, James -- Kosaka, Takayuki -- Holmes, Alison J -- Rogers, Andrew M -- Cappuzzo, Federico -- Mok, Tony -- Lee, Charles -- Johnson, Bruce E -- Cantley, Lewis C -- Janne, Pasi A -- 1K12CA87723-01/CA/NCI NIH HHS/ -- GM41890/GM/NIGMS NIH HHS/ -- K08CA120060-01/CA/NCI NIH HHS/ -- P01 CA089021/CA/NCI NIH HHS/ -- P20CA90578-02/CA/NCI NIH HHS/ -- R01 GM041890/GM/NIGMS NIH HHS/ -- R01-CA111560/CA/NCI NIH HHS/ -- R01CA114465-01/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2007 May 18;316(5827):1039-43. Epub 2007 Apr 26.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Massachusetts General Hospital Cancer Center, Boston, MA 02114, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17463250" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antineoplastic Agents/pharmacology/therapeutic use ; CHO Cells ; Carcinoma, Non-Small-Cell Lung/drug therapy/genetics/*metabolism/*pathology ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Cricetinae ; Cricetulus ; Drug Resistance, Neoplasm ; Enzyme Inhibitors ; *Gene Amplification ; Humans ; Indoles/pharmacology ; Lung Neoplasms/drug therapy/genetics/metabolism/pathology ; Phosphatidylinositol 3-Kinases/metabolism ; Phosphorylation ; Proto-Oncogene Proteins/*genetics/metabolism ; Proto-Oncogene Proteins c-akt/metabolism ; Proto-Oncogene Proteins c-met ; Quinazolines/*pharmacology/therapeutic use ; Receptor, ErbB-3/*metabolism ; Receptors, Growth Factor/*genetics/metabolism ; *Signal Transduction ; Sulfones/pharmacology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 7
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    Molecular phylogenetics of mastodon and Tyrannosaurus rex (2008)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2008-04-26
    Description: We report a molecular phylogeny for a nonavian dinosaur, extending our knowledge of trait evolution within nonavian dinosaurs into the macromolecular level of biological organization. Fragments of collagen alpha1(I) and alpha2(I) proteins extracted from fossil bones of Tyrannosaurus rex and Mammut americanum (mastodon) were analyzed with a variety of phylogenetic methods. Despite missing sequence data, the mastodon groups with elephant and the T. rex groups with birds, consistent with predictions based on genetic and morphological data for mastodon and on morphological data for T. rex. Our findings suggest that molecular data from long-extinct organisms may have the potential for resolving relationships at critical areas in the vertebrate evolutionary tree that have, so far, been phylogenetically intractable.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Organ, Chris L -- Schweitzer, Mary H -- Zheng, Wenxia -- Freimark, Lisa M -- Cantley, Lewis C -- Asara, John M -- F32 GM075490/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2008 Apr 25;320(5875):499. doi: 10.1126/science.1154284.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Harvard University, Cambridge, MA 02138, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18436782" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Bayes Theorem ; Biological Evolution ; Birds/classification/genetics ; Bone and Bones ; Collagen Type I/*chemistry/genetics ; Dinosaurs/anatomy & histology/*classification/*genetics ; Elephants/anatomy & histology/*classification/*genetics ; Fossils ; Likelihood Functions ; Molecular Sequence Data ; *Phylogeny ; Sequence Alignment
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 8
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    Understanding the Warburg effect: the metabolic requirements of cell proliferation (2009)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2009-05-23
    Description: In contrast to normal differentiated cells, which rely primarily on mitochondrial oxidative phosphorylation to generate the energy needed for cellular processes, most cancer cells instead rely on aerobic glycolysis, a phenomenon termed "the Warburg effect." Aerobic glycolysis is an inefficient way to generate adenosine 5'-triphosphate (ATP), however, and the advantage it confers to cancer cells has been unclear. Here we propose that the metabolism of cancer cells, and indeed all proliferating cells, is adapted to facilitate the uptake and incorporation of nutrients into the biomass (e.g., nucleotides, amino acids, and lipids) needed to produce a new cell. Supporting this idea are recent studies showing that (i) several signaling pathways implicated in cell proliferation also regulate metabolic pathways that incorporate nutrients into biomass; and that (ii) certain cancer-associated mutations enable cancer cells to acquire and metabolize nutrients in a manner conducive to proliferation rather than efficient ATP production. A better understanding of the mechanistic links between cellular metabolism and growth control may ultimately lead to better treatments for human cancer.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2849637/" 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/PMC2849637/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Vander Heiden, Matthew G -- Cantley, Lewis C -- Thompson, Craig B -- R01 CA092660/CA/NCI NIH HHS/ -- R01 CA092660-09/CA/NCI NIH HHS/ -- R01 CA105463/CA/NCI NIH HHS/ -- R01 CA105463-06/CA/NCI NIH HHS/ -- R01 GM056203/GM/NIGMS NIH HHS/ -- T32 CA009172/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2009 May 22;324(5930):1029-33. doi: 10.1126/science.1160809.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19460998" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine Triphosphate/metabolism ; Aerobiosis ; Amino Acids/biosynthesis ; Animals ; *Cell Proliferation ; Glucose/metabolism ; *Glycolysis ; Humans ; Lipids/biosynthesis ; Metabolic Networks and Pathways ; Mutation ; Neoplasms/genetics/*metabolism/*pathology ; Nucleotides/biosynthesis ; Oxidative Phosphorylation ; Signal Transduction
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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