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  4. Monthly Traffic Estimate
  5. How Does Link.springer.com Make Money
  6. Keywords
  7. Topics
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We are analyzing https://link.springer.com/article/10.1186/1475-4924-2-28.

Title:
Complexes between the LKB1 tumor suppressor, STRADα/β and MO25α/β are upstream kinases in the AMP-activated protein kinase cascade | Journal of Biology
Description:
Background The AMP-activated protein kinase (AMPK) cascade is a sensor of cellular energy charge that acts as a
Website Age:
28 years and 1 months (reg. 1997-05-29).

Matching Content Categories {📚}

  • Science
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Content Management System {📝}

What CMS is link.springer.com built with?

Custom-built

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What is the average monthly size of link.springer.com audience?

🌠 Phenomenal Traffic: 5M - 10M visitors per month


Based on our best estimate, this website will receive around 5,000,019 visitors per month in the current month.
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How Does Link.springer.com Make Money? {💸}

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Keywords {🔍}

lkb, ampkk, ampk, protein, cells, kinase, article, activity, pubmed, stradα, figure, activation, google, scholar, domain, catalytic, cas, moα, ampkα, phosphorylation, complexes, kinases, hela, cell, thr, complex, antibody, results, recombinant, expressed, antibodies, activate, amp, previously, wildtype, expression, upstream, ampactivated, activated, gstampkα, antilkb, lanes, purified, buffer, phenformin, substrate, control, hardie, aica, riboside,

Topics {✒️}

5-aminoimidazole-4-carboxamide-1-beta-d-ribofuranoside protein kinase complement gst-tagged wild-type lkb1 stably expressing wild-type gst-tagged kinase-inactive mutant full length gst-ampkα1 full-length gst-ampkα1 ste20-related pseudokinase stradα/β open access license insulin signal transduction castrate-resistant prostate cancer amp-activated protein kinase anti-diabetic drugs rosiglitazone serine/threonine protein kinase hela cell-extract protein retroviral gag-pol genes cold spring harbor article download pdf camp-dependent protein kinase gst-ampkα1 catalytic domain gst-ampkα1-catalytic domain pre-immune control immunoglobulin prepacked q-sepharose columns familial peutz-jeghers syndrome peutz-jeghers syndrome locus calmodulin-dependent protein kinase coomassie-blue-stained gels cyclin-dependent kinase inhibitor anti-ampkα1 catalytic domain wild-type lkb1 correlated infra-red laser scanner peutz-jeghers cancer syndrome plasmids encoding myc-ampkα1 untransfected hek-293t cells gst-α1 catalytic domain protein kinase cascade full size image adenine nucleotide-independent mechanism expressed wild-type lkb1 lkb1-null cell line kinase-inactive mutant lkb1 protein g-sepharose beads 4–12% bis-tris gels kinase-dead lkb1 mutant phosphospecific anti-pt172 antibody wild-type fibroblasts lkb1-knockout mouse embryos sheep anti-human lkb1 drug 5-aminoimidazole-4-carboxamide international cancer research

Questions {❓}

  • Corton JM, Gillespie JG, Hawley SA, Hardie DG: 5-Aminoimidazole-4-carboxamide ribonucleoside: a specific method for activating AMP-activated protein kinase in intact cells?
  • The identity of the polypeptide labeled '?

Schema {🗺️}

WebPage:
      mainEntity:
         headline:Complexes between the LKB1 tumor suppressor, STRADα/β and MO25α/β are upstream kinases in the AMP-activated protein kinase cascade
         description:The AMP-activated protein kinase (AMPK) cascade is a sensor of cellular energy charge that acts as a 'metabolic master switch' and inhibits cell proliferation. Activation requires phosphorylation of Thr172 of AMPK within the activation loop by upstream kinases (AMPKKs) that have not been identified. Recently, we identified three related protein kinases acting upstream of the yeast homolog of AMPK. Although they do not have obvious mammalian homologs, they are related to LKB1, a tumor suppressor that is mutated in the human Peutz-Jeghers cancer syndrome. We recently showed that LKB1 exists as a complex with two accessory subunits, STRADα/β and MO25α/β. We report the following observations. First, two AMPKK activities purified from rat liver contain LKB1, STRADα and MO25α, and can be immunoprecipitated using anti-LKB1 antibodies. Second, both endogenous and recombinant complexes of LKB1, STRADα/β and MO25α/β activate AMPK via phosphorylation of Thr172. Third, catalytically active LKB1, STRADα or STRADβ and MO25α or MO25β are required for full activity. Fourth, the AMPK-activating drugs AICA riboside and phenformin do not activate AMPK in HeLa cells (which lack LKB1), but activation can be restored by stably expressing wild-type, but not catalytically inactive, LKB1. Fifth, AICA riboside and phenformin fail to activate AMPK in immortalized fibroblasts from LKB1-knockout mouse embryos. These results provide the first description of a physiological substrate for the LKB1 tumor suppressor and suggest that it functions as an upstream regulator of AMPK. Our findings indicate that the tumors in Peutz-Jeghers syndrome could result from deficient activation of AMPK as a consequence of LKB1 inactivation.
         datePublished:2003-09-24T00:00:00Z
         dateModified:2003-09-24T00:00:00Z
         pageStart:1
         pageEnd:16
         sameAs:https://doi.org/10.1186/1475-4924-2-28
         keywords:
            HeLa Cell
            Additional Data File
            Phenformin
            Upstream Kinase
            Phosphospecific Antibody
            Life Sciences
            general
            Biomedicine
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         isPartOf:
            name:Journal of Biology
            issn:
               1475-4924
            volumeNumber:2
            type:
               Periodical
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            name:BioMed Central
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               type:ImageObject
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               name:Simon A Hawley
               affiliation:
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                     address:
                        name:Division of Molecular Physiology, Wellcome Trust Biocentre, University of Dundee, Dundee, UK
                        type:PostalAddress
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               name:Jérôme Boudeau
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                     name:University of Dundee
                     address:
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                        type:PostalAddress
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               name:Jennifer L Reid
               affiliation:
                     name:University of Dundee
                     address:
                        name:Division of Molecular Physiology, Wellcome Trust Biocentre, University of Dundee, Dundee, UK
                        type:PostalAddress
                     type:Organization
               type:Person
               name:Kirsty J Mustard
               affiliation:
                     name:University of Dundee
                     address:
                        name:Division of Molecular Physiology, Wellcome Trust Biocentre, University of Dundee, Dundee, UK
                        type:PostalAddress
                     type:Organization
               type:Person
               name:Lina Udd
               affiliation:
                     name:University of Helsinki
                     address:
                        name:Molecular Cancer Biology Program, Institute of Biomedicine and Helsinki University Central Hospital, Biomedicum Helsinki, University of Helsinki, Finland
                        type:PostalAddress
                     type:Organization
               type:Person
               name:Tomi P Mäkelä
               affiliation:
                     name:University of Helsinki
                     address:
                        name:Molecular Cancer Biology Program, Institute of Biomedicine and Helsinki University Central Hospital, Biomedicum Helsinki, University of Helsinki, Finland
                        type:PostalAddress
                     type:Organization
               type:Person
               name:Dario R Alessi
               affiliation:
                     name:University of Dundee
                     address:
                        name:MRC Protein Phosphorylation Unit, Wellcome Trust Biocentre, University of Dundee, Dundee, UK
                        type:PostalAddress
                     type:Organization
               email:[email protected]
               type:Person
               name:D Grahame Hardie
               affiliation:
                     name:University of Dundee
                     address:
                        name:Division of Molecular Physiology, Wellcome Trust Biocentre, University of Dundee, Dundee, UK
                        type:PostalAddress
                     type:Organization
               email:[email protected]
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ScholarlyArticle:
      headline:Complexes between the LKB1 tumor suppressor, STRADα/β and MO25α/β are upstream kinases in the AMP-activated protein kinase cascade
      description:The AMP-activated protein kinase (AMPK) cascade is a sensor of cellular energy charge that acts as a 'metabolic master switch' and inhibits cell proliferation. Activation requires phosphorylation of Thr172 of AMPK within the activation loop by upstream kinases (AMPKKs) that have not been identified. Recently, we identified three related protein kinases acting upstream of the yeast homolog of AMPK. Although they do not have obvious mammalian homologs, they are related to LKB1, a tumor suppressor that is mutated in the human Peutz-Jeghers cancer syndrome. We recently showed that LKB1 exists as a complex with two accessory subunits, STRADα/β and MO25α/β. We report the following observations. First, two AMPKK activities purified from rat liver contain LKB1, STRADα and MO25α, and can be immunoprecipitated using anti-LKB1 antibodies. Second, both endogenous and recombinant complexes of LKB1, STRADα/β and MO25α/β activate AMPK via phosphorylation of Thr172. Third, catalytically active LKB1, STRADα or STRADβ and MO25α or MO25β are required for full activity. Fourth, the AMPK-activating drugs AICA riboside and phenformin do not activate AMPK in HeLa cells (which lack LKB1), but activation can be restored by stably expressing wild-type, but not catalytically inactive, LKB1. Fifth, AICA riboside and phenformin fail to activate AMPK in immortalized fibroblasts from LKB1-knockout mouse embryos. These results provide the first description of a physiological substrate for the LKB1 tumor suppressor and suggest that it functions as an upstream regulator of AMPK. Our findings indicate that the tumors in Peutz-Jeghers syndrome could result from deficient activation of AMPK as a consequence of LKB1 inactivation.
      datePublished:2003-09-24T00:00:00Z
      dateModified:2003-09-24T00:00:00Z
      pageStart:1
      pageEnd:16
      sameAs:https://doi.org/10.1186/1475-4924-2-28
      keywords:
         HeLa Cell
         Additional Data File
         Phenformin
         Upstream Kinase
         Phosphospecific Antibody
         Life Sciences
         general
         Biomedicine
      image:
         https://media.springernature.com/lw1200/springer-static/image/art%3A10.1186%2F1475-4924-2-28/MediaObjects/13061_2003_Article_35_Fig1_HTML.jpg
         https://media.springernature.com/lw1200/springer-static/image/art%3A10.1186%2F1475-4924-2-28/MediaObjects/13061_2003_Article_35_Fig2_HTML.jpg
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      isPartOf:
         name:Journal of Biology
         issn:
            1475-4924
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         type:
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      publisher:
         name:BioMed Central
         logo:
            url:https://www.springernature.com/app-sn/public/images/logo-springernature.png
            type:ImageObject
         type:Organization
      author:
            name:Simon A Hawley
            affiliation:
                  name:University of Dundee
                  address:
                     name:Division of Molecular Physiology, Wellcome Trust Biocentre, University of Dundee, Dundee, UK
                     type:PostalAddress
                  type:Organization
            type:Person
            name:Jérôme Boudeau
            affiliation:
                  name:University of Dundee
                  address:
                     name:MRC Protein Phosphorylation Unit, Wellcome Trust Biocentre, University of Dundee, Dundee, UK
                     type:PostalAddress
                  type:Organization
            type:Person
            name:Jennifer L Reid
            affiliation:
                  name:University of Dundee
                  address:
                     name:Division of Molecular Physiology, Wellcome Trust Biocentre, University of Dundee, Dundee, UK
                     type:PostalAddress
                  type:Organization
            type:Person
            name:Kirsty J Mustard
            affiliation:
                  name:University of Dundee
                  address:
                     name:Division of Molecular Physiology, Wellcome Trust Biocentre, University of Dundee, Dundee, UK
                     type:PostalAddress
                  type:Organization
            type:Person
            name:Lina Udd
            affiliation:
                  name:University of Helsinki
                  address:
                     name:Molecular Cancer Biology Program, Institute of Biomedicine and Helsinki University Central Hospital, Biomedicum Helsinki, University of Helsinki, Finland
                     type:PostalAddress
                  type:Organization
            type:Person
            name:Tomi P Mäkelä
            affiliation:
                  name:University of Helsinki
                  address:
                     name:Molecular Cancer Biology Program, Institute of Biomedicine and Helsinki University Central Hospital, Biomedicum Helsinki, University of Helsinki, Finland
                     type:PostalAddress
                  type:Organization
            type:Person
            name:Dario R Alessi
            affiliation:
                  name:University of Dundee
                  address:
                     name:MRC Protein Phosphorylation Unit, Wellcome Trust Biocentre, University of Dundee, Dundee, UK
                     type:PostalAddress
                  type:Organization
            email:[email protected]
            type:Person
            name:D Grahame Hardie
            affiliation:
                  name:University of Dundee
                  address:
                     name:Division of Molecular Physiology, Wellcome Trust Biocentre, University of Dundee, Dundee, UK
                     type:PostalAddress
                  type:Organization
            email:[email protected]
            type:Person
      isAccessibleForFree:1
["Periodical","PublicationVolume"]:
      name:Journal of Biology
      issn:
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      volumeNumber:2
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      name:BioMed Central
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      name:University of Dundee
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      address:
         name:MRC Protein Phosphorylation Unit, Wellcome Trust Biocentre, University of Dundee, Dundee, UK
         type:PostalAddress
      name:University of Dundee
      address:
         name:Division of Molecular Physiology, Wellcome Trust Biocentre, University of Dundee, Dundee, UK
         type:PostalAddress
      name:University of Dundee
      address:
         name:Division of Molecular Physiology, Wellcome Trust Biocentre, University of Dundee, Dundee, UK
         type:PostalAddress
      name:University of Helsinki
      address:
         name:Molecular Cancer Biology Program, Institute of Biomedicine and Helsinki University Central Hospital, Biomedicum Helsinki, University of Helsinki, Finland
         type:PostalAddress
      name:University of Helsinki
      address:
         name:Molecular Cancer Biology Program, Institute of Biomedicine and Helsinki University Central Hospital, Biomedicum Helsinki, University of Helsinki, Finland
         type:PostalAddress
      name:University of Dundee
      address:
         name:MRC Protein Phosphorylation Unit, Wellcome Trust Biocentre, University of Dundee, Dundee, UK
         type:PostalAddress
      name:University of Dundee
      address:
         name:Division of Molecular Physiology, Wellcome Trust Biocentre, University of Dundee, Dundee, UK
         type:PostalAddress
ImageObject:
      url:https://www.springernature.com/app-sn/public/images/logo-springernature.png
Person:
      name:Simon A Hawley
      affiliation:
            name:University of Dundee
            address:
               name:Division of Molecular Physiology, Wellcome Trust Biocentre, University of Dundee, Dundee, UK
               type:PostalAddress
            type:Organization
      name:Jérôme Boudeau
      affiliation:
            name:University of Dundee
            address:
               name:MRC Protein Phosphorylation Unit, Wellcome Trust Biocentre, University of Dundee, Dundee, UK
               type:PostalAddress
            type:Organization
      name:Jennifer L Reid
      affiliation:
            name:University of Dundee
            address:
               name:Division of Molecular Physiology, Wellcome Trust Biocentre, University of Dundee, Dundee, UK
               type:PostalAddress
            type:Organization
      name:Kirsty J Mustard
      affiliation:
            name:University of Dundee
            address:
               name:Division of Molecular Physiology, Wellcome Trust Biocentre, University of Dundee, Dundee, UK
               type:PostalAddress
            type:Organization
      name:Lina Udd
      affiliation:
            name:University of Helsinki
            address:
               name:Molecular Cancer Biology Program, Institute of Biomedicine and Helsinki University Central Hospital, Biomedicum Helsinki, University of Helsinki, Finland
               type:PostalAddress
            type:Organization
      name:Tomi P Mäkelä
      affiliation:
            name:University of Helsinki
            address:
               name:Molecular Cancer Biology Program, Institute of Biomedicine and Helsinki University Central Hospital, Biomedicum Helsinki, University of Helsinki, Finland
               type:PostalAddress
            type:Organization
      name:Dario R Alessi
      affiliation:
            name:University of Dundee
            address:
               name:MRC Protein Phosphorylation Unit, Wellcome Trust Biocentre, University of Dundee, Dundee, UK
               type:PostalAddress
            type:Organization
      email:[email protected]
      name:D Grahame Hardie
      affiliation:
            name:University of Dundee
            address:
               name:Division of Molecular Physiology, Wellcome Trust Biocentre, University of Dundee, Dundee, UK
               type:PostalAddress
            type:Organization
      email:[email protected]
PostalAddress:
      name:Division of Molecular Physiology, Wellcome Trust Biocentre, University of Dundee, Dundee, UK
      name:MRC Protein Phosphorylation Unit, Wellcome Trust Biocentre, University of Dundee, Dundee, UK
      name:Division of Molecular Physiology, Wellcome Trust Biocentre, University of Dundee, Dundee, UK
      name:Division of Molecular Physiology, Wellcome Trust Biocentre, University of Dundee, Dundee, UK
      name:Molecular Cancer Biology Program, Institute of Biomedicine and Helsinki University Central Hospital, Biomedicum Helsinki, University of Helsinki, Finland
      name:Molecular Cancer Biology Program, Institute of Biomedicine and Helsinki University Central Hospital, Biomedicum Helsinki, University of Helsinki, Finland
      name:MRC Protein Phosphorylation Unit, Wellcome Trust Biocentre, University of Dundee, Dundee, UK
      name:Division of Molecular Physiology, Wellcome Trust Biocentre, University of Dundee, Dundee, UK

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