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  • Humans  (14)
  • LUNAR AND PLANETARY EXPLORATION  (9)
  • tyrosine kinase
  • 1995-1999  (13)
  • 1985-1989  (12)
  • 1
    Electronic Resource
    Electronic Resource
    New York, N.Y. : Wiley-Blackwell
    Journal of Cellular Biochemistry 39 (1989), S. 429-441 
    ISSN: 0730-2312
    Keywords: transmembrane signal ; protein phosphorylation ; tyrosine kinase ; signal transmission ; phosphorylation cascade ; Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Insulin stimulated autophosphorylation of the β-subunit of the insulin receptor purified from Fao hepatoma cells or purified from Chinese hamster ovary (CHO/HIRC) or Swiss 3T3 (3T3/HIRC) cells transfected with the wild-type human insulin receptor cDNA. Autophosphorylation of the purified receptor occurred in at least two regions of the β-subunit: the regulatory region containing Tyr-1146, Tyr-1150, and Tyr-1151, and the C-terminus containing Tyr-1316 and Tyr-1322. In the presence of antiphosphotyrosine antibody (α-PY), autophosphorylation of the purified receptor was inhibited nearly 80% during insulin stimulation. Tryptic peptide mapping showed that α-PY inhibited autophosphorylation of both tyrosyl residues in the C-terminus and one tyrosyl residue in the regulatory region, either Tyr-1150 or Tyr-1151. Thus, a bis-phosphorylated form of the regulatory region accumulated in the presence of α-PY, which contained Tyr(P)-1146 and either Tyr(P)-1150 or 1151. In intact Fao, CHO/HIRC, and 3T3/HIRC cells, insulin stimulated tyrosyl phosphorylation of the β-subunit of the insulin receptor. Tryptic peptide mapping indicated that the regulatory region of the β-subunit was mainly (〉80%) bis-phosphorylated; however, all three tyrosyl residues of the regulatory region were phosphorylated in about 20% of the receptors. As the phosphotransferase was activated by tris-phosphorylation but not bis-phosphorylation of the regulatory region of the β-subunit (White et al.: Journal of Biological Chemistry 263:2969-2980, 1988), the extent of autophosphorylation in the regulatory region may play an important regulatory role during signal transmission in the intact cell.
    Additional Material: 5 Ill.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    New York, N.Y. : Wiley-Blackwell
    Journal of Cellular Biochemistry 33 (1987), S. 15-26 
    ISSN: 0730-2312
    Keywords: phosphorylation ; insulin receptor ; tyrosine kinase ; phosphofructokinase ; glycolysis ; Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Various glycolytic and gluconeogenic enzymes were tested as substrates for the insulin receptor kinase. Phosphofructokinase and phosphoglycerate mutase were found to be the best substrates. Phosphorylation of these enzymes was rapid, stimulated 2- to 6-fold by 10-7 M insulin and occurred exclusively on tyrosine residues. Enolase, fructose 1,6-bisphosphatase, lactate dehydrogenases in decreasing order, were also subject to insulin-stimulated phosphorylation but to a smaller extent than that for phpsphofructokinase or phosphoglycerate mutase.The phosphorylation of phosphofructokinase was studied most extensively since phosphofructokinase is known to catalyze a rate-limiting step in glycolosis. The apparent Km of the insulin receptor for phosphofructokinase was 0.1 μM, which is within the physiologic range of concentration of this enzyme in most cells. Tyrosine phosphorylation of phosphofructokinase paralleled autophosphorylation of the β-subunit of the insulin receptor with respect to time course, insulin dose response (half maximal effect between 10-9 and 10-8 M insulin), and cation requirement (Mn2+ 〉 Mg2+ 〉 〉 Ca2+). Further study will be required to determine whether the tyrosine phosphorylation of phosphofructokinase plays a role in insulin-stimulated increases in glycolytic flux.
    Additional Material: 7 Ill.
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  • 3
    Publication Date: 1999-10-26
    Description: Cerebral deposition of amyloid beta peptide (Abeta) is an early and critical feature of Alzheimer's disease. Abeta generation depends on proteolytic cleavage of the amyloid precursor protein (APP) by two unknown proteases: beta-secretase and gamma-secretase. These proteases are prime therapeutic targets. A transmembrane aspartic protease with all the known characteristics of beta-secretase was cloned and characterized. Overexpression of this protease, termed BACE (for beta-site APP-cleaving enzyme) increased the amount of beta-secretase cleavage products, and these were cleaved exactly and only at known beta-secretase positions. Antisense inhibition of endogenous BACE messenger RNA decreased the amount of beta-secretase cleavage products, and purified BACE protein cleaved APP-derived substrates with the same sequence specificity as beta-secretase. Finally, the expression pattern and subcellular localization of BACE were consistent with that expected for beta-secretase. Future development of BACE inhibitors may prove beneficial for the treatment of Alzheimer's disease.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Vassar, R -- Bennett, B D -- Babu-Khan, S -- Kahn, S -- Mendiaz, E A -- Denis, P -- Teplow, D B -- Ross, S -- Amarante, P -- Loeloff, R -- Luo, Y -- Fisher, S -- Fuller, J -- Edenson, S -- Lile, J -- Jarosinski, M A -- Biere, A L -- Curran, E -- Burgess, T -- Louis, J C -- Collins, F -- Treanor, J -- Rogers, G -- Citron, M -- New York, N.Y. -- Science. 1999 Oct 22;286(5440):735-41.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Amgen, Inc., One Amgen Center Drive, M/S 29-2-B, Thousand Oaks, CA 91320-1799, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10531052" target="_blank"〉PubMed〈/a〉
    Keywords: Alzheimer Disease/drug therapy/*enzymology ; Amino Acid Motifs ; Amino Acid Sequence ; Amyloid Precursor Protein Secretases ; Amyloid beta-Peptides/*biosynthesis ; Amyloid beta-Protein Precursor/*metabolism ; Animals ; Aspartic Acid Endopeptidases/chemistry/genetics/*isolation & ; purification/*metabolism ; Binding Sites ; Brain/enzymology/metabolism ; Cell Line ; Cloning, Molecular ; Endopeptidases ; Endosomes/enzymology ; Gene Expression ; Gene Library ; Golgi Apparatus/enzymology ; Humans ; Hydrogen-Ion Concentration ; Molecular Sequence Data ; Oligonucleotides, Antisense/pharmacology ; Peptides/metabolism ; Protease Inhibitors/pharmacology ; RNA, Messenger/genetics/metabolism ; Recombinant Fusion Proteins/metabolism ; Transfection
    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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  • 4
    Publication Date: 1999-09-18
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Fuller, B P -- Kahn, M J -- Barr, P A -- Biesecker, L -- Crowley, E -- Garber, J -- Mansoura, M K -- Murphy, P -- Murray, J -- Phillips, J -- Rothenberg, K -- Rothstein, M -- Stopfer, J -- Swergold, G -- Weber, B -- Collins, F K -- Hudson, K L -- New York, N.Y. -- Science. 1999 Aug 27;285(5432):1359-61.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉barbaraf@exchange.nih.gov〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10490410" target="_blank"〉PubMed〈/a〉
    Keywords: *Bioethics ; *Confidentiality ; *Disclosure ; Ethics Committees, Research ; Federal Government ; *Genetic Privacy ; *Genetic Research ; *Genetics, Medical ; Government Regulation ; Humans ; Informed Consent ; Privacy ; Research/legislation & jurisprudence/*standards ; *Research Subjects ; United States
    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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  • 5
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1989-07-07
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kahn, C R -- Goldstein, B J -- New York, N.Y. -- Science. 1989 Jul 7;245(4913):13.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2662406" target="_blank"〉PubMed〈/a〉
    Keywords: Diabetes Mellitus/*physiopathology ; Humans ; Insulin/*physiology ; Insulin Resistance
    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
    Publication Date: 1997-03-21
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rothenberg, K -- Fuller, B -- Rothstein, M -- Duster, T -- Ellis Kahn, M J -- Cunningham, R -- Fine, B -- Hudson, K -- King, M C -- Murphy, P -- Swergold, G -- Collins, F -- New York, N.Y. -- Science. 1997 Mar 21;275(5307):1755-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Law and Health Care Program, University of Maryland School of Law, 500 West Baltimore Street, Baltimore, MD 21201, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9122681" target="_blank"〉PubMed〈/a〉
    Keywords: Confidentiality ; Disclosure ; Employment/*legislation & jurisprudence ; Federal Government ; Genetic Diseases, Inborn ; *Genetic Privacy ; *Genetic Testing ; *Genetics, Medical ; *Government Regulation ; Humans ; Insurance Selection Bias ; Insurance, Health/legislation & jurisprudence ; *Prejudice ; *Public Policy ; United States
    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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  • 7
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1997-01-03
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kahn, P -- New York, N.Y. -- Science. 1997 Jan 3;275(5296):25-6.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8999529" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Australia ; Biotechnology/*economics ; Financing, Government ; *Genetics, Medical ; *Genome, Human ; Genotype ; Human Genome Project/*economics ; Humans ; Mutation ; *Research Support as Topic ; Sequence Analysis, DNA
    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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  • 8
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1997-07-11
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kahn, P -- Gibbons, A -- New York, N.Y. -- Science. 1997 Jul 11;277(5323):176-8.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9235628" target="_blank"〉PubMed〈/a〉
    Keywords: Africa ; Animals ; Base Sequence ; *Biological Evolution ; DNA, Mitochondrial/*genetics/isolation & purification ; Hominidae/*genetics ; Humans ; Mutation ; Polymerase Chain Reaction ; Sequence Analysis, DNA ; Sequence Homology, Nucleic Acid
    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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  • 9
    Publication Date: 1995-10-20
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hudson, K L -- Rothenberg, K H -- Andrews, L B -- Kahn, M J -- Collins, F S -- New York, N.Y. -- Science. 1995 Oct 20;270(5235):391-3.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7569991" target="_blank"〉PubMed〈/a〉
    Keywords: Federal Government ; Genetic Diseases, Inborn ; *Genetics, Medical ; Government Regulation ; Guidelines as Topic ; *Health Care Reform ; Health Services Accessibility ; Human Genome Project ; Humans ; *Insurance Selection Bias ; *Insurance, Health/legislation & jurisprudence ; *Medically Uninsured ; United States
    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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  • 10
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1995-10-20
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kahn, P -- New York, N.Y. -- Science. 1995 Oct 20;270(5235):369-70.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7569989" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Bacterial Proteins/analysis/chemistry/genetics ; Computer Communication Networks ; Databases, Factual ; *Electrophoresis, Gel, Two-Dimensional ; Escherichia coli/chemistry/genetics ; Fungal Proteins/analysis/chemistry/genetics ; Genes, Fungal ; Humans ; Mass Spectrometry/*methods ; Proteins/*analysis/chemistry/genetics ; Saccharomyces cerevisiae/chemistry/genetics ; Software
    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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