Inhibition of glycogen synthase kinase-3 by insulin mediated by protein kinase B View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

1995-12

AUTHORS

Darren A. E. Cross, Dario R. Alessi, Philip Cohen, Mirjana Andjelkovich, Brian A. Hemmings

ABSTRACT

GLYCOGEN synthase kinase-3 (GSK3)1 is implicated in the regulation of several physiological processes, including the control of glycogen2 and protein3 synthesis by insulin, modulation of the transcription factors AP-1 and CREB4–6, the specification of cell fate in Drosophila7 and dorsoventral patterning in Xenopus embryos8. GSK3 is inhibited by serine phosphorylation in response to insulin or growth factors3,9–11 and in vitro by either MAP kinase-activated protein (MAPKAP) kinase-1 (also known as p90rsk) or p70 ribosomal S6 kinase (p70S6k)12,13. Here we show, however, that agents which prevent the activation of both MAPKAP kinase-1 and p70S6k by insulin in vivo do not block the phosphorylation and inhibition of GSK3. Another insulin-stimulated protein kinase inactivates GSK3 under these conditions, and we demonstrate that it is the product of the proto-oncogene protein kinase B (PKB, also known as Akt/RAC). Like the inhibition of GSK3 (refs 10, 14), the activation of PKB is prevented by inhibitors of phosphatidylinositol (PI) 3-kinase. More... »

PAGES

785-789

Journal

TITLE

Nature

ISSUE

6559

VOLUME

378

Related Patents

  • Methods Of Treating Gastrointestinal Stromal Tumors
  • Pharmaceutical Compositions Comprising A Tungsten Salt (Vi) For The Treatment Of Neurodegenerative Disorders, Particularly Alzheimer's Disease And Schizophrenia
  • Methods, Kits, And Compositions For Stem Cell Self-Renewal
  • Adiponectin Receptor-Activating Compound
  • Rac-Proteine Kinase As Therapeutic Agent Or In Diagnostics
  • Methods Of Treating Gastrointestinal Stromal Tumors
  • Arylaminoalcohol-Substituted 2,3-Dihydroimidazo[1,2-C]Quinolines
  • Useful For The Modulation Of Kinase Activity Of C-Abl, C-Kit, Vegfr, Pdgfr, Flt-3, C-Met, Her Family, Raf Kinase Family And Disease Polymorphs Thereof; Hyperproliferative Diseases, Cancer; 1-(5-(4-(1h-Pyrazol-4-Yl)Pyrimidin-2-Yloxy)-2-Fluorophenyl)-3-(3-Isopropyl-1-(Quinolin-6-Yl)-1h-Pyrazol-5-Yl)Urea
  • Nucleotide Sequences Coding Polypeptide For Use In The Treatment Of Myocardial Necrosis Or Ischemia Reperfusion Injuries
  • Akt Ligands And Polynucleotides Encoding Akt Ligands
  • Polypeptides Biodrugs With Given Amino Acid Sequence Which Includes Phosphorylated Serine Or Threonine; Type Ii Diabetes And Alzheimer's Disease
  • Methods And Compositions For Stem Cell Self-Renewal
  • Methods Of Treating Gastrointestinal Stromal Tumors
  • Glycogen Synthase Kinase-3 Inhibitors
  • Methods And Compositions For Stem Cell Self-Renewal
  • Dihydronaphthyridines And Related Compounds Useful As Kinase Inhibitors For The Treatment Of Proliferative Diseases
  • Small Molecule Antagonists Of Phosphatidylinositol-3,4,5-Triphosphate (Pip3) And Uses Thereof
  • Use Of Substituted 2,3-Dihydroimidazo[1,2-C]Quinazolines For Treating Lymphomas
  • Compositions Of 1-(4-Bromo-5-(1-Ethyl-7-(Methylamino)-2-Oxo-1,2-Dihydro-1,6-Naphthyridin-3-Yl)-2-Fluorophenyl)-3-Phenylurea
  • 2—Amino—N— [7—Methoxy—2, 3-Dihydroimidazo-[1, 2-C] Quinazolin-5-Yl] Pyrimidine—5—Carboxamides
  • 3-(4-(3-Guanidinophenyl)-1,2,3-Triazol-1-Yl)Benzyl Phosphoric Acid Hydrochloride; Obesity, Non-Insulin Dependent Diabetes Mellitus, Insulin-Dependent Condition, Affective Disorder, Neurodegenerative Diseases, Psychotic Disease; Compounds Having Hydrophobic Moiety To A Terminus Of A Peptide Gsk-3
  • Human Akt3 Nucleic Acid And Uses Thereof
  • Alkoxy-Substituted 2,3-Dihydroimidazo[1,2-C]Quinazolines
  • Heterocyclic Enzyme Inhibitors
  • Antidiabetic Agents; Alzheimer's Disease
  • Tyrosisne Kinase Inhibitors Such As N-[4-(6-Dibenzofuran-4-Yl-Pyrimidin-4-Ylamino)-Phenyl]-4-Morpholin-4-Yl-Benzamide, Used As Anticasrcinogenic Or Antoproliferative Agents, Especially In The Treatment Of Breast Cancer
  • Urea Substituted With A 5 Member Nitrogen-Containing Ring; Biological Conjugated Drug Used To Modulate Of The Activation State Of P38 Kinase Protein; Antiinflammatory Agents; Rheumatoid Arthritis, Asthma, Sepsis, Toxic Shock Syndrome, Adult Respiratory Distress Syndrome, Stroke, Reperfusion Injury
  • Use Of Substituted 2,3-Dihydroimidazo[1,2-C]Quinazolines For The Treatment Of Myeloma
  • Aminoalcohol Substituted 2,3-Dihydroimidazo[1,2-C]Quinazoline Derivatives Useful For Treating Hyper-Proliferative Disorders And Diseases Associated With Angiogenesis
  • Methods And Compositions For Stem Cell Self-Renewal
  • Akt Ligands And Polynucleotides Encoding Akt Ligands
  • Dihydropyridopyrimidinyl, Dihydronaphthyidinyl And Related Compounds Useful As Kinase Inhibitors For The Treatment Of Proliferative Diseases
  • Small Molecule Antagonists Of Phosphatidylinositol-3,4,5-Triphosphate (Pip3) And Uses Thereof
  • Pharmaceutical Compositions Comprising A Tungsten Salt (Vi) For The Treatment Of Neurodegenerative Disorders, Particularly Alzheimer's Disease And Schizophrenia
  • Tumour Suppressor And Uses Thereof
  • Disease Caused By C-Abl Kinase, C-Kit Kinase, Oncogenic Forms, Aberrant Fusion Proteins And Polymorphs; 1-(3-T-Butylisoxazol-5-Yl)-3-(2-Fluoro-4-(2-(1-Methyl-1h-Pyrazol-4-Yl)Pyridin-4-Yloxy)Phenyl)Urea
  • For Treatment Diabetes In A Human Or Animal Subject
  • Akt Ligands And Polynucleotides Encoding Akt Ligands
  • Methods Of Treating Gastrointestinal Stromal Tumors
  • Methods And Products Relating To Gsk3Β Regulation
  • Control Of Protein Synthesis, And Screening Method For Agents
  • Inhibitors Of Glycogen Synthase Kinase 3
  • Reperfusion With Omega-3 Glycerides Promotes Donor Organ Protection For Transplantation
  • N-Acyl Ureas Exhibiting Anti-Cancer And Anti-Proliferative Activities
  • Alkoxy-Substituted 2,3-Dihydroimidazo[1,2-C]Quinazolines
  • Dihydronaphthyridines And Related Compounds Useful As Kinase Inhibitors For The Treatment Of Proliferative Diseases
  • Methods And Compositions Related To Regulation Of Cytokine Production By Glycogen Synthase Kinase 3 (Gsk-3)
  • Adduct Comprising A Molecule Binding With A Kinase; Antiinflammatory Agents; Modulating Activation State Of P38 Kinase Protein; Switch Control Ligands To Induce Or Restrict Conformation
  • Use Of Substituted 2,3-Dihydroimidazo[1,2-C]Quinazolines
  • Methods Of Treating Gastrointestinal Stromal Tumors
  • Enzyme Modulators And Treatments
  • Akt Nucleic Acids, Polypeptides, And Uses Thereof
  • Use Of Substituted 2,3-Dihydroimidazo[1,2-C]Quinazolines
  • Treatment, Prevention, And Reversal Of Alcohol-Induced Liver Disease
  • Amorphous Kinase Inhibitor Formulations And Methods Of Use Thereof
  • Polypeptides That Inhibit Dopamine D2 Receptor-Disc1 Interaction And Methods Of Use Thereof
  • Inhibitors Of Glycogen Synthase Kinase 3
  • Inhibitors Of Glycogen Synthase Kinase 3
  • Adding Compound Suspected Of Effecting Glycogen Synthase Kinase 3 Beta (Gsk-3 Beta ) To Cells; Adding An Inflammatory Molecule; Measuring Determinant Of Gsk- 3 Beta
  • Glycogen Synthase Kinase-3 Inhibitors
  • Akt Ligands And Polynucleotides Encoding Akt Ligands
  • Combinations Of Substituted 2,3-Dihydroimidazo[1,2-C]Quinazolines
  • Inhibitors Of Glycogen Synthase Kinase-3 And Methods For Identifying And Using The Same
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/378785a0

    DOI

    http://dx.doi.org/10.1038/378785a0

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1042289302

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/8524413


    Indexing Status Check whether this publication has been indexed by Scopus and Web Of Science using the SN Indexing Status Tool
    Incoming Citations Browse incoming citations for this publication using opencitations.net

    JSON-LD is the canonical representation for SciGraph data.

    TIP: You can open this SciGraph record using an external JSON-LD service: JSON-LD Playground Google SDTT

    [
      {
        "@context": "https://springernature.github.io/scigraph/jsonld/sgcontext.json", 
        "about": [
          {
            "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/06", 
            "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
            "name": "Biological Sciences", 
            "type": "DefinedTerm"
          }, 
          {
            "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/0601", 
            "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
            "name": "Biochemistry and Cell Biology", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "3T3 Cells", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Amino Acid Sequence", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Animals", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Calcium-Calmodulin-Dependent Protein Kinases", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Cells, Cultured", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Enzyme Activation", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Glycogen Synthase Kinase 3", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Glycogen Synthase Kinases", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Mice", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Microtubule-Associated Proteins", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Molecular Sequence Data", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Muscles", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Phosphorylation", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Protein Serine-Threonine Kinases", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Proto-Oncogene Proteins", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Proto-Oncogene Proteins c-akt", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Ribosomal Protein S6 Kinases", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Serine", 
            "type": "DefinedTerm"
          }
        ], 
        "author": [
          {
            "affiliation": {
              "alternateName": "MRC Protein Phosphorylation Unit, Department of Biochemistry, University of Dundee, DD1 4HN, Dundee, UK", 
              "id": "http://www.grid.ac/institutes/grid.451071.6", 
              "name": [
                "MRC Protein Phosphorylation Unit, Department of Biochemistry, University of Dundee, DD1 4HN, Dundee, UK"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Cross", 
            "givenName": "Darren A. E.", 
            "id": "sg:person.01332612771.51", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01332612771.51"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "MRC Protein Phosphorylation Unit, Department of Biochemistry, University of Dundee, DD1 4HN, Dundee, UK", 
              "id": "http://www.grid.ac/institutes/grid.451071.6", 
              "name": [
                "MRC Protein Phosphorylation Unit, Department of Biochemistry, University of Dundee, DD1 4HN, Dundee, UK"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Alessi", 
            "givenName": "Dario R.", 
            "id": "sg:person.0740015144.50", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0740015144.50"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "MRC Protein Phosphorylation Unit, Department of Biochemistry, University of Dundee, DD1 4HN, Dundee, UK", 
              "id": "http://www.grid.ac/institutes/grid.451071.6", 
              "name": [
                "MRC Protein Phosphorylation Unit, Department of Biochemistry, University of Dundee, DD1 4HN, Dundee, UK"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Cohen", 
            "givenName": "Philip", 
            "id": "sg:person.016345545202.71", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.016345545202.71"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Friedrich Miescher Institute, CH 4002, Basel, Switzerland", 
              "id": "http://www.grid.ac/institutes/grid.482245.d", 
              "name": [
                "Friedrich Miescher Institute, CH 4002, Basel, Switzerland"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Andjelkovich", 
            "givenName": "Mirjana", 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Friedrich Miescher Institute, CH 4002, Basel, Switzerland", 
              "id": "http://www.grid.ac/institutes/grid.482245.d", 
              "name": [
                "Friedrich Miescher Institute, CH 4002, Basel, Switzerland"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Hemmings", 
            "givenName": "Brian A.", 
            "id": "sg:person.0706331530.34", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0706331530.34"
            ], 
            "type": "Person"
          }
        ], 
        "citation": [
          {
            "id": "sg:pub.10.1038/376599a0", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1019263292", 
              "https://doi.org/10.1038/376599a0"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/358070a0", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1037308118", 
              "https://doi.org/10.1038/358070a0"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/374617a0", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1046370946", 
              "https://doi.org/10.1038/374617a0"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/348302a0", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1038265672", 
              "https://doi.org/10.1038/348302a0"
            ], 
            "type": "CreativeWork"
          }
        ], 
        "datePublished": "1995-12", 
        "datePublishedReg": "1995-12-01", 
        "description": "GLYCOGEN synthase kinase-3 (GSK3)1 is implicated in the regulation of several physiological processes, including the control of glycogen2 and protein3 synthesis by insulin, modulation of the transcription factors AP-1 and CREB4\u20136, the specification of cell fate in Drosophila7 and dorsoventral patterning in Xenopus embryos8. GSK3 is inhibited by serine phosphorylation in response to insulin or growth factors3,9\u201311 and in vitro by either MAP kinase-activated protein (MAPKAP) kinase-1 (also known as p90rsk) or p70 ribosomal S6 kinase (p70S6k)12,13. Here we show, however, that agents which prevent the activation of both MAPKAP kinase-1 and p70S6k by insulin in vivo do not block the phosphorylation and inhibition of GSK3. Another insulin-stimulated protein kinase inactivates GSK3 under these conditions, and we demonstrate that it is the product of the proto-oncogene protein kinase B (PKB, also known as Akt/RAC). Like the inhibition of GSK3 (refs 10, 14), the activation of PKB is prevented by inhibitors of phosphatidylinositol (PI) 3-kinase.", 
        "genre": "article", 
        "id": "sg:pub.10.1038/378785a0", 
        "isAccessibleForFree": false, 
        "isPartOf": [
          {
            "id": "sg:journal.1018957", 
            "issn": [
              "0028-0836", 
              "1476-4687"
            ], 
            "name": "Nature", 
            "publisher": "Springer Nature", 
            "type": "Periodical"
          }, 
          {
            "issueNumber": "6559", 
            "type": "PublicationIssue"
          }, 
          {
            "type": "PublicationVolume", 
            "volumeNumber": "378"
          }
        ], 
        "keywords": [
          "glycogen synthase kinase-3", 
          "inhibition of GSK3", 
          "synthase kinase-3", 
          "protein kinase B", 
          "MAP kinase-activated protein kinase-1", 
          "kinase 3", 
          "kinase B", 
          "kinase 1", 
          "MAPKAP kinase-1", 
          "p70 ribosomal S6 kinase", 
          "activation of PKB", 
          "ribosomal S6 kinase", 
          "transcription factor AP-1", 
          "protein kinase 1", 
          "inhibitor of phosphatidylinositol", 
          "factor AP-1", 
          "dorsoventral patterning", 
          "cell fate", 
          "S6 kinase", 
          "serine phosphorylation", 
          "physiological processes", 
          "GSK3", 
          "AP-1", 
          "phosphatidylinositol", 
          "phosphorylation", 
          "inhibition", 
          "activation", 
          "PKB", 
          "kinase", 
          "p70S6k", 
          "regulation", 
          "patterning", 
          "fate", 
          "insulin", 
          "proto", 
          "vivo", 
          "inhibitors", 
          "modulation", 
          "response", 
          "synthesis", 
          "agents", 
          "products", 
          "process", 
          "control", 
          "conditions", 
          "specification"
        ], 
        "name": "Inhibition of glycogen synthase kinase-3 by insulin mediated by protein kinase B", 
        "pagination": "785-789", 
        "productId": [
          {
            "name": "dimensions_id", 
            "type": "PropertyValue", 
            "value": [
              "pub.1042289302"
            ]
          }, 
          {
            "name": "doi", 
            "type": "PropertyValue", 
            "value": [
              "10.1038/378785a0"
            ]
          }, 
          {
            "name": "pubmed_id", 
            "type": "PropertyValue", 
            "value": [
              "8524413"
            ]
          }
        ], 
        "sameAs": [
          "https://doi.org/10.1038/378785a0", 
          "https://app.dimensions.ai/details/publication/pub.1042289302"
        ], 
        "sdDataset": "articles", 
        "sdDatePublished": "2022-11-24T20:47", 
        "sdLicense": "https://scigraph.springernature.com/explorer/license/", 
        "sdPublisher": {
          "name": "Springer Nature - SN SciGraph project", 
          "type": "Organization"
        }, 
        "sdSource": "s3://com-springernature-scigraph/baseset/20221124/entities/gbq_results/article/article_266.jsonl", 
        "type": "ScholarlyArticle", 
        "url": "https://doi.org/10.1038/378785a0"
      }
    ]
     

    Download the RDF metadata as:  json-ld nt turtle xml License info

    HOW TO GET THIS DATA PROGRAMMATICALLY:

    JSON-LD is a popular format for linked data which is fully compatible with JSON.

    curl -H 'Accept: application/ld+json' 'https://scigraph.springernature.com/pub.10.1038/378785a0'

    N-Triples is a line-based linked data format ideal for batch operations.

    curl -H 'Accept: application/n-triples' 'https://scigraph.springernature.com/pub.10.1038/378785a0'

    Turtle is a human-readable linked data format.

    curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1038/378785a0'

    RDF/XML is a standard XML format for linked data.

    curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1038/378785a0'


     

    This table displays all metadata directly associated to this object as RDF triples.

    225 TRIPLES      21 PREDICATES      94 URIs      82 LITERALS      25 BLANK NODES

    Subject Predicate Object
    1 sg:pub.10.1038/378785a0 schema:about N13ac96ef82674e08bdcca983fd180d2c
    2 N204aac7cb33f4b4f88ea07d503fac476
    3 N27bf67cafddf4a5e84298e081fe40924
    4 N29c61cb4f7574859b7b2d8dbae8696f3
    5 N33c3c7f6ce2548ae9c27f44c072b9f51
    6 N436eab5ec962446e82257175a8c51da2
    7 N5ceeee94437d429dbf0ead68e363f547
    8 N75ea3c1fcdd3481493c5919a5eed2f18
    9 N7a7f679a8f6f4140811a856d703fa03a
    10 N8df05d674d8e4671bd72d6583f39a1ef
    11 N9aebdb907e87487abd60dcf82b504eaa
    12 Na62c5364f54b43248e3f632d74979042
    13 Nb8397c66f3c54272802d5962d2914e22
    14 Nc56c43683eee4f30ba85eef7ecf361a9
    15 Nc64e091f8a2840adaa20521fc7d38817
    16 Nd31ef1a1152c4259aac0ce01a7c40ef1
    17 Nd83d44dedeea48e0af5ca80265c6e6b7
    18 Ne6b4400402e24f48bafb3f42c970d659
    19 anzsrc-for:06
    20 anzsrc-for:0601
    21 schema:author N5768ede8315e4ba98ca3e3555f4837ab
    22 schema:citation sg:pub.10.1038/348302a0
    23 sg:pub.10.1038/358070a0
    24 sg:pub.10.1038/374617a0
    25 sg:pub.10.1038/376599a0
    26 schema:datePublished 1995-12
    27 schema:datePublishedReg 1995-12-01
    28 schema:description GLYCOGEN synthase kinase-3 (GSK3)1 is implicated in the regulation of several physiological processes, including the control of glycogen2 and protein3 synthesis by insulin, modulation of the transcription factors AP-1 and CREB4–6, the specification of cell fate in Drosophila7 and dorsoventral patterning in Xenopus embryos8. GSK3 is inhibited by serine phosphorylation in response to insulin or growth factors3,9–11 and in vitro by either MAP kinase-activated protein (MAPKAP) kinase-1 (also known as p90rsk) or p70 ribosomal S6 kinase (p70S6k)12,13. Here we show, however, that agents which prevent the activation of both MAPKAP kinase-1 and p70S6k by insulin in vivo do not block the phosphorylation and inhibition of GSK3. Another insulin-stimulated protein kinase inactivates GSK3 under these conditions, and we demonstrate that it is the product of the proto-oncogene protein kinase B (PKB, also known as Akt/RAC). Like the inhibition of GSK3 (refs 10, 14), the activation of PKB is prevented by inhibitors of phosphatidylinositol (PI) 3-kinase.
    29 schema:genre article
    30 schema:isAccessibleForFree false
    31 schema:isPartOf N47fa4cc8d3f24d59b0cc6424ded1f195
    32 Nc0e3930ec29644f8834a76f8ff4cbab0
    33 sg:journal.1018957
    34 schema:keywords AP-1
    35 GSK3
    36 MAP kinase-activated protein kinase-1
    37 MAPKAP kinase-1
    38 PKB
    39 S6 kinase
    40 activation
    41 activation of PKB
    42 agents
    43 cell fate
    44 conditions
    45 control
    46 dorsoventral patterning
    47 factor AP-1
    48 fate
    49 glycogen synthase kinase-3
    50 inhibition
    51 inhibition of GSK3
    52 inhibitor of phosphatidylinositol
    53 inhibitors
    54 insulin
    55 kinase
    56 kinase 1
    57 kinase 3
    58 kinase B
    59 modulation
    60 p70 ribosomal S6 kinase
    61 p70S6k
    62 patterning
    63 phosphatidylinositol
    64 phosphorylation
    65 physiological processes
    66 process
    67 products
    68 protein kinase 1
    69 protein kinase B
    70 proto
    71 regulation
    72 response
    73 ribosomal S6 kinase
    74 serine phosphorylation
    75 specification
    76 synthase kinase-3
    77 synthesis
    78 transcription factor AP-1
    79 vivo
    80 schema:name Inhibition of glycogen synthase kinase-3 by insulin mediated by protein kinase B
    81 schema:pagination 785-789
    82 schema:productId N173fd6049fce426cab9daf4877e77c2a
    83 N64bebde919b543a9b9f49ac0ffda59b6
    84 N7a2d5c0926514fac996eeca9e9c46aee
    85 schema:sameAs https://app.dimensions.ai/details/publication/pub.1042289302
    86 https://doi.org/10.1038/378785a0
    87 schema:sdDatePublished 2022-11-24T20:47
    88 schema:sdLicense https://scigraph.springernature.com/explorer/license/
    89 schema:sdPublisher Nca3e320dee5a4825b3ad976bac2f0e18
    90 schema:url https://doi.org/10.1038/378785a0
    91 sgo:license sg:explorer/license/
    92 sgo:sdDataset articles
    93 rdf:type schema:ScholarlyArticle
    94 N13ac96ef82674e08bdcca983fd180d2c schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    95 schema:name Mice
    96 rdf:type schema:DefinedTerm
    97 N173fd6049fce426cab9daf4877e77c2a schema:name pubmed_id
    98 schema:value 8524413
    99 rdf:type schema:PropertyValue
    100 N204aac7cb33f4b4f88ea07d503fac476 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    101 schema:name Enzyme Activation
    102 rdf:type schema:DefinedTerm
    103 N27bf67cafddf4a5e84298e081fe40924 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    104 schema:name Ribosomal Protein S6 Kinases
    105 rdf:type schema:DefinedTerm
    106 N289eca7c62cb4c44871063cfa27b47f6 rdf:first sg:person.0740015144.50
    107 rdf:rest Nf82905c9b41d4343961b0ab270931f59
    108 N29c61cb4f7574859b7b2d8dbae8696f3 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    109 schema:name Glycogen Synthase Kinase 3
    110 rdf:type schema:DefinedTerm
    111 N33c3c7f6ce2548ae9c27f44c072b9f51 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    112 schema:name Glycogen Synthase Kinases
    113 rdf:type schema:DefinedTerm
    114 N3611156b8ace4704b97652894dfbd752 rdf:first sg:person.0706331530.34
    115 rdf:rest rdf:nil
    116 N436eab5ec962446e82257175a8c51da2 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    117 schema:name Microtubule-Associated Proteins
    118 rdf:type schema:DefinedTerm
    119 N47fa4cc8d3f24d59b0cc6424ded1f195 schema:issueNumber 6559
    120 rdf:type schema:PublicationIssue
    121 N5768ede8315e4ba98ca3e3555f4837ab rdf:first sg:person.01332612771.51
    122 rdf:rest N289eca7c62cb4c44871063cfa27b47f6
    123 N5ceeee94437d429dbf0ead68e363f547 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    124 schema:name Cells, Cultured
    125 rdf:type schema:DefinedTerm
    126 N64bebde919b543a9b9f49ac0ffda59b6 schema:name doi
    127 schema:value 10.1038/378785a0
    128 rdf:type schema:PropertyValue
    129 N75ea3c1fcdd3481493c5919a5eed2f18 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    130 schema:name Calcium-Calmodulin-Dependent Protein Kinases
    131 rdf:type schema:DefinedTerm
    132 N7a2d5c0926514fac996eeca9e9c46aee schema:name dimensions_id
    133 schema:value pub.1042289302
    134 rdf:type schema:PropertyValue
    135 N7a7f679a8f6f4140811a856d703fa03a schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    136 schema:name Protein Serine-Threonine Kinases
    137 rdf:type schema:DefinedTerm
    138 N8df05d674d8e4671bd72d6583f39a1ef schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    139 schema:name Muscles
    140 rdf:type schema:DefinedTerm
    141 N9aebdb907e87487abd60dcf82b504eaa schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    142 schema:name Animals
    143 rdf:type schema:DefinedTerm
    144 Na62c5364f54b43248e3f632d74979042 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    145 schema:name Serine
    146 rdf:type schema:DefinedTerm
    147 Nb2579a55d452497ca5dc8a87cf85bd95 rdf:first Nf554819128bb436eb4d6f654ff22738f
    148 rdf:rest N3611156b8ace4704b97652894dfbd752
    149 Nb8397c66f3c54272802d5962d2914e22 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    150 schema:name Molecular Sequence Data
    151 rdf:type schema:DefinedTerm
    152 Nc0e3930ec29644f8834a76f8ff4cbab0 schema:volumeNumber 378
    153 rdf:type schema:PublicationVolume
    154 Nc56c43683eee4f30ba85eef7ecf361a9 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    155 schema:name Amino Acid Sequence
    156 rdf:type schema:DefinedTerm
    157 Nc64e091f8a2840adaa20521fc7d38817 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    158 schema:name Phosphorylation
    159 rdf:type schema:DefinedTerm
    160 Nca3e320dee5a4825b3ad976bac2f0e18 schema:name Springer Nature - SN SciGraph project
    161 rdf:type schema:Organization
    162 Nd31ef1a1152c4259aac0ce01a7c40ef1 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    163 schema:name Proto-Oncogene Proteins
    164 rdf:type schema:DefinedTerm
    165 Nd83d44dedeea48e0af5ca80265c6e6b7 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    166 schema:name Proto-Oncogene Proteins c-akt
    167 rdf:type schema:DefinedTerm
    168 Ne6b4400402e24f48bafb3f42c970d659 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    169 schema:name 3T3 Cells
    170 rdf:type schema:DefinedTerm
    171 Nf554819128bb436eb4d6f654ff22738f schema:affiliation grid-institutes:grid.482245.d
    172 schema:familyName Andjelkovich
    173 schema:givenName Mirjana
    174 rdf:type schema:Person
    175 Nf82905c9b41d4343961b0ab270931f59 rdf:first sg:person.016345545202.71
    176 rdf:rest Nb2579a55d452497ca5dc8a87cf85bd95
    177 anzsrc-for:06 schema:inDefinedTermSet anzsrc-for:
    178 schema:name Biological Sciences
    179 rdf:type schema:DefinedTerm
    180 anzsrc-for:0601 schema:inDefinedTermSet anzsrc-for:
    181 schema:name Biochemistry and Cell Biology
    182 rdf:type schema:DefinedTerm
    183 sg:journal.1018957 schema:issn 0028-0836
    184 1476-4687
    185 schema:name Nature
    186 schema:publisher Springer Nature
    187 rdf:type schema:Periodical
    188 sg:person.01332612771.51 schema:affiliation grid-institutes:grid.451071.6
    189 schema:familyName Cross
    190 schema:givenName Darren A. E.
    191 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01332612771.51
    192 rdf:type schema:Person
    193 sg:person.016345545202.71 schema:affiliation grid-institutes:grid.451071.6
    194 schema:familyName Cohen
    195 schema:givenName Philip
    196 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.016345545202.71
    197 rdf:type schema:Person
    198 sg:person.0706331530.34 schema:affiliation grid-institutes:grid.482245.d
    199 schema:familyName Hemmings
    200 schema:givenName Brian A.
    201 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0706331530.34
    202 rdf:type schema:Person
    203 sg:person.0740015144.50 schema:affiliation grid-institutes:grid.451071.6
    204 schema:familyName Alessi
    205 schema:givenName Dario R.
    206 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0740015144.50
    207 rdf:type schema:Person
    208 sg:pub.10.1038/348302a0 schema:sameAs https://app.dimensions.ai/details/publication/pub.1038265672
    209 https://doi.org/10.1038/348302a0
    210 rdf:type schema:CreativeWork
    211 sg:pub.10.1038/358070a0 schema:sameAs https://app.dimensions.ai/details/publication/pub.1037308118
    212 https://doi.org/10.1038/358070a0
    213 rdf:type schema:CreativeWork
    214 sg:pub.10.1038/374617a0 schema:sameAs https://app.dimensions.ai/details/publication/pub.1046370946
    215 https://doi.org/10.1038/374617a0
    216 rdf:type schema:CreativeWork
    217 sg:pub.10.1038/376599a0 schema:sameAs https://app.dimensions.ai/details/publication/pub.1019263292
    218 https://doi.org/10.1038/376599a0
    219 rdf:type schema:CreativeWork
    220 grid-institutes:grid.451071.6 schema:alternateName MRC Protein Phosphorylation Unit, Department of Biochemistry, University of Dundee, DD1 4HN, Dundee, UK
    221 schema:name MRC Protein Phosphorylation Unit, Department of Biochemistry, University of Dundee, DD1 4HN, Dundee, UK
    222 rdf:type schema:Organization
    223 grid-institutes:grid.482245.d schema:alternateName Friedrich Miescher Institute, CH 4002, Basel, Switzerland
    224 schema:name Friedrich Miescher Institute, CH 4002, Basel, Switzerland
    225 rdf:type schema:Organization
     




    Preview window. Press ESC to close (or click here)


    ...