The isoform-specific stretch of hSos1 defines a new Grb2-binding domain View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2000-11-30

AUTHORS

Natasha Zarich, José Luis Oliva, Rocío Jorge, Eugenio Santos, José M Rojas

ABSTRACT

hSos1 isoform II, defined by the presence of a 15 amino acid stretch in its carboxy-terminal region, exhibits higher Grb2 affinity than hSos1 isoform I. In this study, we investigated the cause for this difference and observed that, in addition to the four currently accepted Grb2-binding motifs, a number of additional, putative SH3-minimal binding sites (SH3-MBS) could be identified. The isoform II-specific 15 amino acid stretch contained one of them. Indeed, we demonstrated by site-directed mutagenesis that these SH3-MBS were responsible for the Grb2 interaction, and we found that C-terminal fragments of the two hSos1 isoforms (lacking the four cannonical Grb2-binding motifs, but containing the SH3-minimal binding sites) were able to bind Grb2, with the isoform II fragment showing higher Grb2 affinity than the corresponding isoform I fragment. Furthermore, we provide evidence that C-terminal truncated mutants of either hSos1 isoform, containing only the SH3-minimal binding sites, were able to originate in vivo stable complexes with Grb2. Although, Grb2-binding remains higher in both full-length isoforms, compared to the C-terminal truncated mutants, these mutants were also able to activate Ras, supporting a potential role of this C-terminal region as negative modulator of Sos1 activity. These findings document the existence of a new, functional, SH3-minimal binding site located in the specific stretch of hSos1 isoform II which may be responsible for the increased Grb2 affinity of this isoform in comparison to isoform I, and for the physiological properties differences between both isoforms. Moreover, these SH3-minimal binding sites may be sufficient to attain stable and functional hSos1-Grb2 complexes. More... »

PAGES

5872-5883

References to SciGraph publications

  • 1992-12. Association of the Shc and Grb2/Sem5 SH2-containing proteins is implicated in activation of the Ras pathway by tyrosine kinases in NATURE
  • 1993-09. Influence of fluconazole on antipyrine kinetics in rats in EUROPEAN JOURNAL OF DRUG METABOLISM AND PHARMACOKINETICS
  • 1994-04-01. Critical residues in an SH3 domain from Sem-5 suggest a mechanism for proline-rich peptide recognition in NATURE STRUCTURAL & MOLECULAR BIOLOGY
  • 1999-03-04. Isoform-specific insertion near the Grb2-binding domain modulates the intrinsic guanine nucleotide exchange activity of hSos1 in ONCOGENE
  • 1998-05-21. Activation of Ras and its downstream extracellular signal-regulated protein kinases by the CDC25 homology domain of mouse Son-of-sevenless 1 (mSos1) in ONCOGENE
  • 1995-07. The Grb2 binding domain of mSos1 is not required for downstream signal transduction in NATURE GENETICS
  • 1993-10. The pathway to signal achievement in NATURE
  • 1995-02. Protein modules and signalling networks in NATURE
  • 1997-08. Ras effectors and their role in mitogenesis and oncogenesis in JOURNAL OF MOLECULAR MEDICINE
  • 1998-09-17. From Src Homology domains to other signaling modules: proposal of the `protein recognition code' in ONCOGENE
  • 1993-05. The SH2 and SH3 domains of mammalian Grb2 couple the EGF receptor to the Ras activator mSos1 in NATURE
  • 1993-12-16. Proteins regulating Ras and its relatives in NATURE
  • 1998-02-05. Transformation suppressor activity of C3G is independent of its CDC25-homology domain in ONCOGENE
  • 1998-07. The structural basis of the activation of Ras by Sos in NATURE
  • 1993-05. How receptors turn Ras on in NATURE
  • 1993-05. Guanine-nucleotide-releasing factor hSos1 binds to Grb2 and links receptor tyrosine kinases to Ras signalling in NATURE
  • 1998-08-27. Effector domain mutants of Rho dissociate cytoskeletal changes from nuclear signaling and cellular transformation in ONCOGENE
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/sj.onc.1203955

    DOI

    http://dx.doi.org/10.1038/sj.onc.1203955

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1047740454

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/11127818


    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/2008/11", 
            "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
            "name": "Medical and Health Sciences", 
            "type": "DefinedTerm"
          }, 
          {
            "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/1103", 
            "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
            "name": "Clinical Sciences", 
            "type": "DefinedTerm"
          }, 
          {
            "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/1112", 
            "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
            "name": "Oncology and Carcinogenesis", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "3T3 Cells", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Adaptor Proteins, Signal Transducing", 
            "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": "Binding Sites", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "COS Cells", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Chlorocebus aethiops", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "GRB2 Adaptor Protein", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Glutathione Transferase", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Humans", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Mice", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Molecular Sequence Data", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Mutagenesis, Site-Directed", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Peptide Fragments", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Polymerase Chain Reaction", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Protein Isoforms", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Protein Structure, Tertiary", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Proteins", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Recombinant Fusion Proteins", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "SOS1 Protein", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Saccharomyces cerevisiae", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Substrate Specificity", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "src Homology Domains", 
            "type": "DefinedTerm"
          }
        ], 
        "author": [
          {
            "affiliation": {
              "alternateName": "Unidad de Biolog\u00eda Celular, Centro Nacional de Biolog\u00eda Fundamental, Instituto de Salud Carlos III, 28220, Madrid, Majadahonda, Spain", 
              "id": "http://www.grid.ac/institutes/grid.413448.e", 
              "name": [
                "Unidad de Biolog\u00eda Celular, Centro Nacional de Biolog\u00eda Fundamental, Instituto de Salud Carlos III, 28220, Madrid, Majadahonda, Spain"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Zarich", 
            "givenName": "Natasha", 
            "id": "sg:person.0707261110.08", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0707261110.08"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Unidad de Biolog\u00eda Celular, Centro Nacional de Biolog\u00eda Fundamental, Instituto de Salud Carlos III, 28220, Madrid, Majadahonda, Spain", 
              "id": "http://www.grid.ac/institutes/grid.413448.e", 
              "name": [
                "Unidad de Biolog\u00eda Celular, Centro Nacional de Biolog\u00eda Fundamental, Instituto de Salud Carlos III, 28220, Madrid, Majadahonda, Spain"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Oliva", 
            "givenName": "Jos\u00e9 Luis", 
            "id": "sg:person.0755374310.20", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0755374310.20"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Unidad de Biolog\u00eda Celular, Centro Nacional de Biolog\u00eda Fundamental, Instituto de Salud Carlos III, 28220, Madrid, Majadahonda, Spain", 
              "id": "http://www.grid.ac/institutes/grid.413448.e", 
              "name": [
                "Unidad de Biolog\u00eda Celular, Centro Nacional de Biolog\u00eda Fundamental, Instituto de Salud Carlos III, 28220, Madrid, Majadahonda, Spain"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Jorge", 
            "givenName": "Roc\u00edo", 
            "id": "sg:person.01011534260.38", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01011534260.38"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "IBM-CC, CSIC-USAL. Campus Unamuno, Universidad de Salamanca, 37007, Salamanca, Spain", 
              "id": "http://www.grid.ac/institutes/grid.11762.33", 
              "name": [
                "Laboratory of Cellular and Molecular Biology, National Cancer Institute, National Institutes of Health, MD 20892, Bethesda, Maryland, USA", 
                "IBM-CC, CSIC-USAL. Campus Unamuno, Universidad de Salamanca, 37007, Salamanca, Spain"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Santos", 
            "givenName": "Eugenio", 
            "id": "sg:person.01065110724.36", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01065110724.36"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Unidad de Biolog\u00eda Celular, Centro Nacional de Biolog\u00eda Fundamental, Instituto de Salud Carlos III, 28220, Madrid, Majadahonda, Spain", 
              "id": "http://www.grid.ac/institutes/grid.413448.e", 
              "name": [
                "Unidad de Biolog\u00eda Celular, Centro Nacional de Biolog\u00eda Fundamental, Instituto de Salud Carlos III, 28220, Madrid, Majadahonda, Spain"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Rojas", 
            "givenName": "Jos\u00e9 M", 
            "id": "sg:person.013461756342.19", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.013461756342.19"
            ], 
            "type": "Person"
          }
        ], 
        "citation": [
          {
            "id": "sg:pub.10.1038/363083a0", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1022031225", 
              "https://doi.org/10.1038/363083a0"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/360689a0", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1042782556", 
              "https://doi.org/10.1038/360689a0"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/sj.onc.1201822", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1003481069", 
              "https://doi.org/10.1038/sj.onc.1201822"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1007/s001090050143", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1037872908", 
              "https://doi.org/10.1007/s001090050143"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/ng0795-294", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1001925125", 
              "https://doi.org/10.1038/ng0795-294"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/sj.onc.1202483", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1020619112", 
              "https://doi.org/10.1038/sj.onc.1202483"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/363015a0", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1023945033", 
              "https://doi.org/10.1038/363015a0"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nsb0494-221", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1046713967", 
              "https://doi.org/10.1038/nsb0494-221"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/sj.onc.1202182", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1001000305", 
              "https://doi.org/10.1038/sj.onc.1202182"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/366643a0", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1005902014", 
              "https://doi.org/10.1038/366643a0"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/373573a0", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1008518821", 
              "https://doi.org/10.1038/373573a0"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1007/bf03188808", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1038450869", 
              "https://doi.org/10.1007/bf03188808"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/sj.onc.1201569", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1018801830", 
              "https://doi.org/10.1038/sj.onc.1201569"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/28548", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1021391978", 
              "https://doi.org/10.1038/28548"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/sj.onc.1202022", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1045636208", 
              "https://doi.org/10.1038/sj.onc.1202022"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/363085a0", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1011022170", 
              "https://doi.org/10.1038/363085a0"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/365781a0", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1020168730", 
              "https://doi.org/10.1038/365781a0"
            ], 
            "type": "CreativeWork"
          }
        ], 
        "datePublished": "2000-11-30", 
        "datePublishedReg": "2000-11-30", 
        "description": "AbstracthSos1 isoform II, defined by the presence of a 15 amino acid stretch in its carboxy-terminal region, exhibits higher Grb2 affinity than hSos1 isoform I. In this study, we investigated the cause for this difference and observed that, in addition to the four currently accepted Grb2-binding motifs, a number of additional, putative SH3-minimal binding sites (SH3-MBS) could be identified. The isoform II-specific 15 amino acid stretch contained one of them. Indeed, we demonstrated by site-directed mutagenesis that these SH3-MBS were responsible for the Grb2 interaction, and we found that C-terminal fragments of the two hSos1 isoforms (lacking the four cannonical Grb2-binding motifs, but containing the SH3-minimal binding sites) were able to bind Grb2, with the isoform II fragment showing higher Grb2 affinity than the corresponding isoform I fragment. Furthermore, we provide evidence that C-terminal truncated mutants of either hSos1 isoform, containing only the SH3-minimal binding sites, were able to originate in vivo stable complexes with Grb2. Although, Grb2-binding remains higher in both full-length isoforms, compared to the C-terminal truncated mutants, these mutants were also able to activate Ras, supporting a potential role of this C-terminal region as negative modulator of Sos1 activity. These findings document the existence of a new, functional, SH3-minimal binding site located in the specific stretch of hSos1 isoform II which may be responsible for the increased Grb2 affinity of this isoform in comparison to isoform I, and for the physiological properties differences between both isoforms. Moreover, these SH3-minimal binding sites may be sufficient to attain stable and functional hSos1-Grb2 complexes.", 
        "genre": "article", 
        "id": "sg:pub.10.1038/sj.onc.1203955", 
        "isAccessibleForFree": false, 
        "isPartOf": [
          {
            "id": "sg:journal.1097543", 
            "issn": [
              "0950-9232", 
              "1476-5594"
            ], 
            "name": "Oncogene", 
            "publisher": "Springer Nature", 
            "type": "Periodical"
          }, 
          {
            "issueNumber": "51", 
            "type": "PublicationIssue"
          }, 
          {
            "type": "PublicationVolume", 
            "volumeNumber": "19"
          }
        ], 
        "keywords": [
          "C-terminal fragment", 
          "potential role", 
          "amino acid stretch", 
          "binding sites", 
          "negative modulator", 
          "isoform II", 
          "full-length isoform", 
          "isoforms", 
          "isoforms I", 
          "Grb2 interaction", 
          "C-terminal", 
          "carboxy-terminal region", 
          "differences", 
          "cause", 
          "hSos1", 
          "Grb2", 
          "affinity", 
          "sites", 
          "findings", 
          "specific stretches", 
          "RA", 
          "evidence", 
          "C-terminal region", 
          "modulator", 
          "activity", 
          "stretch", 
          "study", 
          "site-directed mutagenesis", 
          "role", 
          "fragments", 
          "presence", 
          "mutants", 
          "addition", 
          "region", 
          "number", 
          "comparison", 
          "complexes", 
          "mutagenesis", 
          "interaction", 
          "SH3", 
          "domain", 
          "stable complexes", 
          "SOS1 activity", 
          "motif", 
          "existence", 
          "property differences"
        ], 
        "name": "The isoform-specific stretch of hSos1 defines a new Grb2-binding domain", 
        "pagination": "5872-5883", 
        "productId": [
          {
            "name": "dimensions_id", 
            "type": "PropertyValue", 
            "value": [
              "pub.1047740454"
            ]
          }, 
          {
            "name": "doi", 
            "type": "PropertyValue", 
            "value": [
              "10.1038/sj.onc.1203955"
            ]
          }, 
          {
            "name": "pubmed_id", 
            "type": "PropertyValue", 
            "value": [
              "11127818"
            ]
          }
        ], 
        "sameAs": [
          "https://doi.org/10.1038/sj.onc.1203955", 
          "https://app.dimensions.ai/details/publication/pub.1047740454"
        ], 
        "sdDataset": "articles", 
        "sdDatePublished": "2022-09-02T15:50", 
        "sdLicense": "https://scigraph.springernature.com/explorer/license/", 
        "sdPublisher": {
          "name": "Springer Nature - SN SciGraph project", 
          "type": "Organization"
        }, 
        "sdSource": "s3://com-springernature-scigraph/baseset/20220902/entities/gbq_results/article/article_343.jsonl", 
        "type": "ScholarlyArticle", 
        "url": "https://doi.org/10.1038/sj.onc.1203955"
      }
    ]
     

    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/sj.onc.1203955'

    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/sj.onc.1203955'

    Turtle is a human-readable linked data format.

    curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1038/sj.onc.1203955'

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

    curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1038/sj.onc.1203955'


     

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

    303 TRIPLES      21 PREDICATES      112 URIs      86 LITERALS      30 BLANK NODES

    Subject Predicate Object
    1 sg:pub.10.1038/sj.onc.1203955 schema:about N08f7aecbf34641eaa8b3704aba8143a7
    2 N18a69d42102d4522bc62e343ce9b2867
    3 N28f26b82e5bc47d5904a0465070fcd0d
    4 N30f67a75578f42f39d5d2d5b2566caad
    5 N34d19a95d66e41d686e3be7d737f63fc
    6 N4f3122521f61471f88ff660dbcb4fa44
    7 N50b3a14f5a294d4b90b545a9a39aab5e
    8 N5c6920662be54b009907ae2cebfa7cd9
    9 N5f4dab2a7fc04df389903570cc51dde9
    10 N661b90885ded4641a267f63ea0f9bee0
    11 N68b9efc340884b9f914e4e26bcf07ad0
    12 N71cf66bfa02c4afbb3fab4b1c259e00a
    13 N8100572b8cfb459281e1e9b02ef2182c
    14 N90a33afa75874dd4a0c88338044ff83a
    15 Na26ec1c0b28c48468c39d54501893ecd
    16 Nad3213253c844f8994b5c7cbd75e27fe
    17 Ncad7ebd0f1e84d409231490f72a2cf6f
    18 Nd67536f1e64b4a46813733b98c386740
    19 Nde9ee1ea3b1d42d39397be541477dbeb
    20 Nea76a6b6e91c46a8a689049fb9f8e5a7
    21 Nf45d7a8491fd4423aea69542597b93af
    22 Nf5ef5d14d44a491181142ff44a473bfe
    23 Nfa74603dfc8b48e4bf1641984c3b072c
    24 anzsrc-for:11
    25 anzsrc-for:1103
    26 anzsrc-for:1112
    27 schema:author Ne0667b2935224f99bf8ad3400b450074
    28 schema:citation sg:pub.10.1007/bf03188808
    29 sg:pub.10.1007/s001090050143
    30 sg:pub.10.1038/28548
    31 sg:pub.10.1038/360689a0
    32 sg:pub.10.1038/363015a0
    33 sg:pub.10.1038/363083a0
    34 sg:pub.10.1038/363085a0
    35 sg:pub.10.1038/365781a0
    36 sg:pub.10.1038/366643a0
    37 sg:pub.10.1038/373573a0
    38 sg:pub.10.1038/ng0795-294
    39 sg:pub.10.1038/nsb0494-221
    40 sg:pub.10.1038/sj.onc.1201569
    41 sg:pub.10.1038/sj.onc.1201822
    42 sg:pub.10.1038/sj.onc.1202022
    43 sg:pub.10.1038/sj.onc.1202182
    44 sg:pub.10.1038/sj.onc.1202483
    45 schema:datePublished 2000-11-30
    46 schema:datePublishedReg 2000-11-30
    47 schema:description AbstracthSos1 isoform II, defined by the presence of a 15 amino acid stretch in its carboxy-terminal region, exhibits higher Grb2 affinity than hSos1 isoform I. In this study, we investigated the cause for this difference and observed that, in addition to the four currently accepted Grb2-binding motifs, a number of additional, putative SH3-minimal binding sites (SH3-MBS) could be identified. The isoform II-specific 15 amino acid stretch contained one of them. Indeed, we demonstrated by site-directed mutagenesis that these SH3-MBS were responsible for the Grb2 interaction, and we found that C-terminal fragments of the two hSos1 isoforms (lacking the four cannonical Grb2-binding motifs, but containing the SH3-minimal binding sites) were able to bind Grb2, with the isoform II fragment showing higher Grb2 affinity than the corresponding isoform I fragment. Furthermore, we provide evidence that C-terminal truncated mutants of either hSos1 isoform, containing only the SH3-minimal binding sites, were able to originate in vivo stable complexes with Grb2. Although, Grb2-binding remains higher in both full-length isoforms, compared to the C-terminal truncated mutants, these mutants were also able to activate Ras, supporting a potential role of this C-terminal region as negative modulator of Sos1 activity. These findings document the existence of a new, functional, SH3-minimal binding site located in the specific stretch of hSos1 isoform II which may be responsible for the increased Grb2 affinity of this isoform in comparison to isoform I, and for the physiological properties differences between both isoforms. Moreover, these SH3-minimal binding sites may be sufficient to attain stable and functional hSos1-Grb2 complexes.
    48 schema:genre article
    49 schema:isAccessibleForFree false
    50 schema:isPartOf N8fa60849f5ed4d64acd3419f788942c5
    51 N9a6976d831b84424b3444c54cbb44b61
    52 sg:journal.1097543
    53 schema:keywords C-terminal
    54 C-terminal fragment
    55 C-terminal region
    56 Grb2
    57 Grb2 interaction
    58 RA
    59 SH3
    60 SOS1 activity
    61 activity
    62 addition
    63 affinity
    64 amino acid stretch
    65 binding sites
    66 carboxy-terminal region
    67 cause
    68 comparison
    69 complexes
    70 differences
    71 domain
    72 evidence
    73 existence
    74 findings
    75 fragments
    76 full-length isoform
    77 hSos1
    78 interaction
    79 isoform II
    80 isoforms
    81 isoforms I
    82 modulator
    83 motif
    84 mutagenesis
    85 mutants
    86 negative modulator
    87 number
    88 potential role
    89 presence
    90 property differences
    91 region
    92 role
    93 site-directed mutagenesis
    94 sites
    95 specific stretches
    96 stable complexes
    97 stretch
    98 study
    99 schema:name The isoform-specific stretch of hSos1 defines a new Grb2-binding domain
    100 schema:pagination 5872-5883
    101 schema:productId N3d674063b6dd44e89e7aeb26f5fb60ca
    102 N55483bb0476b4931a95096430591dd58
    103 Nca68965221ff4b05a6e5c7f7f5d9fc9a
    104 schema:sameAs https://app.dimensions.ai/details/publication/pub.1047740454
    105 https://doi.org/10.1038/sj.onc.1203955
    106 schema:sdDatePublished 2022-09-02T15:50
    107 schema:sdLicense https://scigraph.springernature.com/explorer/license/
    108 schema:sdPublisher Nbc4dac5669a040e79da2951d4f86df20
    109 schema:url https://doi.org/10.1038/sj.onc.1203955
    110 sgo:license sg:explorer/license/
    111 sgo:sdDataset articles
    112 rdf:type schema:ScholarlyArticle
    113 N08f7aecbf34641eaa8b3704aba8143a7 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    114 schema:name Glutathione Transferase
    115 rdf:type schema:DefinedTerm
    116 N18a69d42102d4522bc62e343ce9b2867 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    117 schema:name Animals
    118 rdf:type schema:DefinedTerm
    119 N28f26b82e5bc47d5904a0465070fcd0d schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    120 schema:name 3T3 Cells
    121 rdf:type schema:DefinedTerm
    122 N30f67a75578f42f39d5d2d5b2566caad schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    123 schema:name Adaptor Proteins, Signal Transducing
    124 rdf:type schema:DefinedTerm
    125 N34d19a95d66e41d686e3be7d737f63fc schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    126 schema:name Chlorocebus aethiops
    127 rdf:type schema:DefinedTerm
    128 N3bf4d02e3b9148b5af49563a440d91c8 rdf:first sg:person.013461756342.19
    129 rdf:rest rdf:nil
    130 N3d674063b6dd44e89e7aeb26f5fb60ca schema:name doi
    131 schema:value 10.1038/sj.onc.1203955
    132 rdf:type schema:PropertyValue
    133 N4f3122521f61471f88ff660dbcb4fa44 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    134 schema:name Proteins
    135 rdf:type schema:DefinedTerm
    136 N50b3a14f5a294d4b90b545a9a39aab5e schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    137 schema:name src Homology Domains
    138 rdf:type schema:DefinedTerm
    139 N55483bb0476b4931a95096430591dd58 schema:name pubmed_id
    140 schema:value 11127818
    141 rdf:type schema:PropertyValue
    142 N5c6920662be54b009907ae2cebfa7cd9 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    143 schema:name Mutagenesis, Site-Directed
    144 rdf:type schema:DefinedTerm
    145 N5e44c628bae1438294f71a98c1c42d38 rdf:first sg:person.01065110724.36
    146 rdf:rest N3bf4d02e3b9148b5af49563a440d91c8
    147 N5f4dab2a7fc04df389903570cc51dde9 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    148 schema:name Substrate Specificity
    149 rdf:type schema:DefinedTerm
    150 N661b90885ded4641a267f63ea0f9bee0 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    151 schema:name Recombinant Fusion Proteins
    152 rdf:type schema:DefinedTerm
    153 N68b9efc340884b9f914e4e26bcf07ad0 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    154 schema:name Saccharomyces cerevisiae
    155 rdf:type schema:DefinedTerm
    156 N71cf66bfa02c4afbb3fab4b1c259e00a schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    157 schema:name COS Cells
    158 rdf:type schema:DefinedTerm
    159 N7684429cc4f84a22a4dfc661d935b6a0 rdf:first sg:person.01011534260.38
    160 rdf:rest N5e44c628bae1438294f71a98c1c42d38
    161 N8100572b8cfb459281e1e9b02ef2182c schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    162 schema:name Binding Sites
    163 rdf:type schema:DefinedTerm
    164 N8fa60849f5ed4d64acd3419f788942c5 schema:issueNumber 51
    165 rdf:type schema:PublicationIssue
    166 N90a33afa75874dd4a0c88338044ff83a schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    167 schema:name Protein Isoforms
    168 rdf:type schema:DefinedTerm
    169 N91a216f270ea4faeb05181c62498de06 rdf:first sg:person.0755374310.20
    170 rdf:rest N7684429cc4f84a22a4dfc661d935b6a0
    171 N9a6976d831b84424b3444c54cbb44b61 schema:volumeNumber 19
    172 rdf:type schema:PublicationVolume
    173 Na26ec1c0b28c48468c39d54501893ecd schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    174 schema:name Humans
    175 rdf:type schema:DefinedTerm
    176 Nad3213253c844f8994b5c7cbd75e27fe schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    177 schema:name Peptide Fragments
    178 rdf:type schema:DefinedTerm
    179 Nbc4dac5669a040e79da2951d4f86df20 schema:name Springer Nature - SN SciGraph project
    180 rdf:type schema:Organization
    181 Nca68965221ff4b05a6e5c7f7f5d9fc9a schema:name dimensions_id
    182 schema:value pub.1047740454
    183 rdf:type schema:PropertyValue
    184 Ncad7ebd0f1e84d409231490f72a2cf6f schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    185 schema:name Protein Structure, Tertiary
    186 rdf:type schema:DefinedTerm
    187 Nd67536f1e64b4a46813733b98c386740 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    188 schema:name Molecular Sequence Data
    189 rdf:type schema:DefinedTerm
    190 Nde9ee1ea3b1d42d39397be541477dbeb schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    191 schema:name Polymerase Chain Reaction
    192 rdf:type schema:DefinedTerm
    193 Ne0667b2935224f99bf8ad3400b450074 rdf:first sg:person.0707261110.08
    194 rdf:rest N91a216f270ea4faeb05181c62498de06
    195 Nea76a6b6e91c46a8a689049fb9f8e5a7 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    196 schema:name GRB2 Adaptor Protein
    197 rdf:type schema:DefinedTerm
    198 Nf45d7a8491fd4423aea69542597b93af schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    199 schema:name Amino Acid Sequence
    200 rdf:type schema:DefinedTerm
    201 Nf5ef5d14d44a491181142ff44a473bfe schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    202 schema:name Mice
    203 rdf:type schema:DefinedTerm
    204 Nfa74603dfc8b48e4bf1641984c3b072c schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    205 schema:name SOS1 Protein
    206 rdf:type schema:DefinedTerm
    207 anzsrc-for:11 schema:inDefinedTermSet anzsrc-for:
    208 schema:name Medical and Health Sciences
    209 rdf:type schema:DefinedTerm
    210 anzsrc-for:1103 schema:inDefinedTermSet anzsrc-for:
    211 schema:name Clinical Sciences
    212 rdf:type schema:DefinedTerm
    213 anzsrc-for:1112 schema:inDefinedTermSet anzsrc-for:
    214 schema:name Oncology and Carcinogenesis
    215 rdf:type schema:DefinedTerm
    216 sg:journal.1097543 schema:issn 0950-9232
    217 1476-5594
    218 schema:name Oncogene
    219 schema:publisher Springer Nature
    220 rdf:type schema:Periodical
    221 sg:person.01011534260.38 schema:affiliation grid-institutes:grid.413448.e
    222 schema:familyName Jorge
    223 schema:givenName Rocío
    224 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01011534260.38
    225 rdf:type schema:Person
    226 sg:person.01065110724.36 schema:affiliation grid-institutes:grid.11762.33
    227 schema:familyName Santos
    228 schema:givenName Eugenio
    229 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01065110724.36
    230 rdf:type schema:Person
    231 sg:person.013461756342.19 schema:affiliation grid-institutes:grid.413448.e
    232 schema:familyName Rojas
    233 schema:givenName José M
    234 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.013461756342.19
    235 rdf:type schema:Person
    236 sg:person.0707261110.08 schema:affiliation grid-institutes:grid.413448.e
    237 schema:familyName Zarich
    238 schema:givenName Natasha
    239 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0707261110.08
    240 rdf:type schema:Person
    241 sg:person.0755374310.20 schema:affiliation grid-institutes:grid.413448.e
    242 schema:familyName Oliva
    243 schema:givenName José Luis
    244 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0755374310.20
    245 rdf:type schema:Person
    246 sg:pub.10.1007/bf03188808 schema:sameAs https://app.dimensions.ai/details/publication/pub.1038450869
    247 https://doi.org/10.1007/bf03188808
    248 rdf:type schema:CreativeWork
    249 sg:pub.10.1007/s001090050143 schema:sameAs https://app.dimensions.ai/details/publication/pub.1037872908
    250 https://doi.org/10.1007/s001090050143
    251 rdf:type schema:CreativeWork
    252 sg:pub.10.1038/28548 schema:sameAs https://app.dimensions.ai/details/publication/pub.1021391978
    253 https://doi.org/10.1038/28548
    254 rdf:type schema:CreativeWork
    255 sg:pub.10.1038/360689a0 schema:sameAs https://app.dimensions.ai/details/publication/pub.1042782556
    256 https://doi.org/10.1038/360689a0
    257 rdf:type schema:CreativeWork
    258 sg:pub.10.1038/363015a0 schema:sameAs https://app.dimensions.ai/details/publication/pub.1023945033
    259 https://doi.org/10.1038/363015a0
    260 rdf:type schema:CreativeWork
    261 sg:pub.10.1038/363083a0 schema:sameAs https://app.dimensions.ai/details/publication/pub.1022031225
    262 https://doi.org/10.1038/363083a0
    263 rdf:type schema:CreativeWork
    264 sg:pub.10.1038/363085a0 schema:sameAs https://app.dimensions.ai/details/publication/pub.1011022170
    265 https://doi.org/10.1038/363085a0
    266 rdf:type schema:CreativeWork
    267 sg:pub.10.1038/365781a0 schema:sameAs https://app.dimensions.ai/details/publication/pub.1020168730
    268 https://doi.org/10.1038/365781a0
    269 rdf:type schema:CreativeWork
    270 sg:pub.10.1038/366643a0 schema:sameAs https://app.dimensions.ai/details/publication/pub.1005902014
    271 https://doi.org/10.1038/366643a0
    272 rdf:type schema:CreativeWork
    273 sg:pub.10.1038/373573a0 schema:sameAs https://app.dimensions.ai/details/publication/pub.1008518821
    274 https://doi.org/10.1038/373573a0
    275 rdf:type schema:CreativeWork
    276 sg:pub.10.1038/ng0795-294 schema:sameAs https://app.dimensions.ai/details/publication/pub.1001925125
    277 https://doi.org/10.1038/ng0795-294
    278 rdf:type schema:CreativeWork
    279 sg:pub.10.1038/nsb0494-221 schema:sameAs https://app.dimensions.ai/details/publication/pub.1046713967
    280 https://doi.org/10.1038/nsb0494-221
    281 rdf:type schema:CreativeWork
    282 sg:pub.10.1038/sj.onc.1201569 schema:sameAs https://app.dimensions.ai/details/publication/pub.1018801830
    283 https://doi.org/10.1038/sj.onc.1201569
    284 rdf:type schema:CreativeWork
    285 sg:pub.10.1038/sj.onc.1201822 schema:sameAs https://app.dimensions.ai/details/publication/pub.1003481069
    286 https://doi.org/10.1038/sj.onc.1201822
    287 rdf:type schema:CreativeWork
    288 sg:pub.10.1038/sj.onc.1202022 schema:sameAs https://app.dimensions.ai/details/publication/pub.1045636208
    289 https://doi.org/10.1038/sj.onc.1202022
    290 rdf:type schema:CreativeWork
    291 sg:pub.10.1038/sj.onc.1202182 schema:sameAs https://app.dimensions.ai/details/publication/pub.1001000305
    292 https://doi.org/10.1038/sj.onc.1202182
    293 rdf:type schema:CreativeWork
    294 sg:pub.10.1038/sj.onc.1202483 schema:sameAs https://app.dimensions.ai/details/publication/pub.1020619112
    295 https://doi.org/10.1038/sj.onc.1202483
    296 rdf:type schema:CreativeWork
    297 grid-institutes:grid.11762.33 schema:alternateName IBM-CC, CSIC-USAL. Campus Unamuno, Universidad de Salamanca, 37007, Salamanca, Spain
    298 schema:name IBM-CC, CSIC-USAL. Campus Unamuno, Universidad de Salamanca, 37007, Salamanca, Spain
    299 Laboratory of Cellular and Molecular Biology, National Cancer Institute, National Institutes of Health, MD 20892, Bethesda, Maryland, USA
    300 rdf:type schema:Organization
    301 grid-institutes:grid.413448.e schema:alternateName Unidad de Biología Celular, Centro Nacional de Biología Fundamental, Instituto de Salud Carlos III, 28220, Madrid, Majadahonda, Spain
    302 schema:name Unidad de Biología Celular, Centro Nacional de Biología Fundamental, Instituto de Salud Carlos III, 28220, Madrid, Majadahonda, Spain
    303 rdf:type schema:Organization
     




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


    ...