Isoform-specific insertion near the Grb2-binding domain modulates the intrinsic guanine nucleotide exchange activity of hSos1 View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

1999-03-04

AUTHORS

Jose M Rojas, Marianne Subleski, Juan JR Coque, Carmen Guerrero, Rosana Saez, Bao-Qun Li, Eva Lopez, Natasha Zarich, Pilar Aroca, Toru Kamata, Eugenio Santos

ABSTRACT

Two human hSos1 isoforms (Isf I and Isf II; Rojas et al., Oncogene 12, 2291 – 2300, 1996) defined by the presence of a distinct 15 amino acid stretch in one of them, were compared biologically and biochemically using representative NIH3T3 transfectants overexpressing either one. We showed that hSos1-Isf II is significantly more effective than hSos1-Isf I to induce proliferation or malignant transformation of rodent fibroblasts when transfected alone or in conjunction with normal H-Ras (Gly12). The hSos1-Isf II-Ras cotransfectants consistently exhibited higher saturation density, lower cell-doubling times, increased focus-forming activity and higher ability to grow on semisolid medium and at low serum concentration than their hSos1-Isf I-Ras counterparts. Furthermore, the ratio of GTP/GDP bound to cellular p21ras was consistently higher in the hSos1-Isf II-transfected clones, both under basal and stimulated conditions. However, no significant differences were detected in vivo between Isf I- and Isf II-transfected clones regarding the amount, stability and subcellular localization of Sos1-Grb2 complex, or the level of hSos1 phosphorylation upon cellular stimulation. Interestingly, direct Ras guanine nucleotide exchange activity assays in cellular lysates showed that Isf II transfectants consistently exhibited about threefold higher activity than Isf I transfectants under basal, unstimulated conditions. Microinjection into Xenopus oocytes of purified peptides corresponding to the C-terminal region of both isoforms (encompassing the 15 amino acid insertion area and the first Grb2-binding motif) showed that only the Isf II peptide, but not its corresponding Isf I peptide, was able to induce measurable rates of meiotic maturation, and synergyzed with insulin, but not progesterone, in induction of GVBD. Our results suggest that the increased biological potency displayed by hSos1-Isf II is due to higher intrinsic guanine nucleotide exchange activity conferred upon this isoform by the 15 a.a. insertion located in proximity to its Grb2 binding region. More... »

PAGES

1651-1661

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/sj.onc.1202483

DOI

http://dx.doi.org/10.1038/sj.onc.1202483

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1020619112

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/10208427


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": "GRB2 Adaptor Protein", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Guanine Nucleotide Exchange Factors", 
        "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, Insertional", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Protein Isoforms", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Proteins", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Transfection", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Transformation, Genetic", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "ras Guanine Nucleotide Exchange Factors", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "ras Proteins", 
        "type": "DefinedTerm"
      }
    ], 
    "author": [
      {
        "affiliation": {
          "alternateName": "Unidad de Biologia Celular, Centro Nacional de Biologia Fundamental, Instituto de Salud Carlos III, 28220, Majadahonda, Madrid, Spain", 
          "id": "http://www.grid.ac/institutes/grid.413448.e", 
          "name": [
            "Laboratory of Cellular and Molecular Biology, National Cancer Institute, National Institutes of Health, 20892, Bethesda, Maryland, USA", 
            "Unidad de Biologia Celular, Centro Nacional de Biologia Fundamental, Instituto de Salud Carlos III, 28220, Majadahonda, Madrid, Spain"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Rojas", 
        "givenName": "Jose M", 
        "id": "sg:person.013461756342.19", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.013461756342.19"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Laboratory of Biochemical Physiology, NCI-FCRDC, 21071, Frederick, Maryland, USA", 
          "id": "http://www.grid.ac/institutes/grid.418021.e", 
          "name": [
            "Laboratory of Biochemical Physiology, NCI-FCRDC, 21071, Frederick, Maryland, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Subleski", 
        "givenName": "Marianne", 
        "id": "sg:person.01226126661.04", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01226126661.04"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Laboratory of Cellular and Molecular Biology, National Cancer Institute, National Institutes of Health, 20892, Bethesda, Maryland, USA", 
          "id": "http://www.grid.ac/institutes/grid.48336.3a", 
          "name": [
            "Laboratory of Cellular and Molecular Biology, National Cancer Institute, National Institutes of Health, 20892, Bethesda, Maryland, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Coque", 
        "givenName": "Juan JR", 
        "id": "sg:person.01243611424.29", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01243611424.29"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Laboratory of Cellular and Molecular Biology, National Cancer Institute, National Institutes of Health, 20892, Bethesda, Maryland, USA", 
          "id": "http://www.grid.ac/institutes/grid.48336.3a", 
          "name": [
            "Laboratory of Cellular and Molecular Biology, National Cancer Institute, National Institutes of Health, 20892, Bethesda, Maryland, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Guerrero", 
        "givenName": "Carmen", 
        "id": "sg:person.01311724624.43", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01311724624.43"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Laboratory of Cellular and Molecular Biology, National Cancer Institute, National Institutes of Health, 20892, Bethesda, Maryland, USA", 
          "id": "http://www.grid.ac/institutes/grid.48336.3a", 
          "name": [
            "Laboratory of Cellular and Molecular Biology, National Cancer Institute, National Institutes of Health, 20892, Bethesda, Maryland, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Saez", 
        "givenName": "Rosana", 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Laboratory of Biochemical Physiology, NCI-FCRDC, 21071, Frederick, Maryland, USA", 
          "id": "http://www.grid.ac/institutes/grid.418021.e", 
          "name": [
            "Laboratory of Biochemical Physiology, NCI-FCRDC, 21071, Frederick, Maryland, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Li", 
        "givenName": "Bao-Qun", 
        "id": "sg:person.013055461504.59", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.013055461504.59"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Laboratory of Cellular and Molecular Biology, National Cancer Institute, National Institutes of Health, 20892, Bethesda, Maryland, USA", 
          "id": "http://www.grid.ac/institutes/grid.48336.3a", 
          "name": [
            "Laboratory of Cellular and Molecular Biology, National Cancer Institute, National Institutes of Health, 20892, Bethesda, Maryland, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Lopez", 
        "givenName": "Eva", 
        "id": "sg:person.01310602233.41", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01310602233.41"
        ], 
        "type": "Person"
      }, 
      {
        "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": "Laboratory of Cellular and Molecular Biology, National Cancer Institute, National Institutes of Health, 20892, Bethesda, Maryland, USA", 
          "id": "http://www.grid.ac/institutes/grid.48336.3a", 
          "name": [
            "Laboratory of Cellular and Molecular Biology, National Cancer Institute, National Institutes of Health, 20892, Bethesda, Maryland, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Aroca", 
        "givenName": "Pilar", 
        "id": "sg:person.0617471620.87", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0617471620.87"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Laboratory of Biochemical Physiology, NCI-FCRDC, 21071, Frederick, Maryland, USA", 
          "id": "http://www.grid.ac/institutes/grid.418021.e", 
          "name": [
            "Laboratory of Biochemical Physiology, NCI-FCRDC, 21071, Frederick, Maryland, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Kamata", 
        "givenName": "Toru", 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Laboratory of Cellular and Molecular Biology, National Cancer Institute, National Institutes of Health, 20892, Bethesda, Maryland, USA", 
          "id": "http://www.grid.ac/institutes/grid.48336.3a", 
          "name": [
            "Laboratory of Cellular and Molecular Biology, National Cancer Institute, National Institutes of Health, 20892, Bethesda, Maryland, USA"
          ], 
          "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"
      }
    ], 
    "citation": [
      {
        "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.10.1038/363085a0", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1011022170", 
          "https://doi.org/10.1038/363085a0"
        ], 
        "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.10.1038/363045a0", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1051359913", 
          "https://doi.org/10.1038/363045a0"
        ], 
        "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.10.1038/365781a0", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1020168730", 
          "https://doi.org/10.1038/365781a0"
        ], 
        "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.10.1038/363083a0", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1022031225", 
          "https://doi.org/10.1038/363083a0"
        ], 
        "type": "CreativeWork"
      }
    ], 
    "datePublished": "1999-03-04", 
    "datePublishedReg": "1999-03-04", 
    "description": "Two human hSos1 isoforms (Isf\u2009I and Isf\u2009II; Rojas et al., Oncogene 12, 2291\u2009\u2013\u20092300, 1996) defined by the presence of a distinct 15 amino acid stretch in one of them, were compared biologically and biochemically using representative NIH3T3 transfectants overexpressing either one. We showed that hSos1-Isf\u2009II is significantly more effective than hSos1-Isf\u2009I to induce proliferation or malignant transformation of rodent fibroblasts when transfected alone or in conjunction with normal H-Ras (Gly12). The hSos1-Isf\u2009II-Ras cotransfectants consistently exhibited higher saturation density, lower cell-doubling times, increased focus-forming activity and higher ability to grow on semisolid medium and at low serum concentration than their hSos1-Isf\u2009I-Ras counterparts. Furthermore, the ratio of GTP/GDP bound to cellular p21ras was consistently higher in the hSos1-Isf\u2009II-transfected clones, both under basal and stimulated conditions. However, no significant differences were detected in vivo between Isf\u2009I- and Isf\u2009II-transfected clones regarding the amount, stability and subcellular localization of Sos1-Grb2 complex, or the level of hSos1 phosphorylation upon cellular stimulation. Interestingly, direct Ras guanine nucleotide exchange activity assays in cellular lysates showed that Isf\u2009II transfectants consistently exhibited about threefold higher activity than Isf\u2009I transfectants under basal, unstimulated conditions. Microinjection into Xenopus oocytes of purified peptides corresponding to the C-terminal region of both isoforms (encompassing the 15 amino acid insertion area and the first Grb2-binding motif) showed that only the Isf\u2009II peptide, but not its corresponding Isf\u2009I peptide, was able to induce measurable rates of meiotic maturation, and synergyzed with insulin, but not progesterone, in induction of GVBD. Our results suggest that the increased biological potency displayed by hSos1-Isf\u2009II is due to higher intrinsic guanine nucleotide exchange activity conferred upon this isoform by the 15\u2009a.a. insertion located in proximity to its Grb2 binding region.", 
    "genre": "article", 
    "id": "sg:pub.10.1038/sj.onc.1202483", 
    "isAccessibleForFree": false, 
    "isPartOf": [
      {
        "id": "sg:journal.1097543", 
        "issn": [
          "0950-9232", 
          "1476-5594"
        ], 
        "name": "Oncogene", 
        "publisher": "Springer Nature", 
        "type": "Periodical"
      }, 
      {
        "issueNumber": "9", 
        "type": "PublicationIssue"
      }, 
      {
        "type": "PublicationVolume", 
        "volumeNumber": "18"
      }
    ], 
    "keywords": [
      "intrinsic guanine", 
      "low serum concentrations", 
      "amino acid stretch", 
      "C-terminal region", 
      "exchange activity", 
      "normal H-ras", 
      "GTP/GDP", 
      "induction of GVBD", 
      "serum concentrations", 
      "focus-forming activity", 
      "Ras guanine", 
      "malignant transformation", 
      "cell-doubling time", 
      "unstimulated conditions", 
      "subcellular localization", 
      "H-Ras", 
      "NIH3T3 transfectants", 
      "rodent fibroblasts", 
      "cellular lysates", 
      "cellular stimulation", 
      "meiotic maturation", 
      "significant differences", 
      "higher saturation density", 
      "activity assays", 
      "Xenopus oocytes", 
      "Grb2", 
      "semisolid medium", 
      "isoforms", 
      "transfectants", 
      "guanine", 
      "biological potency", 
      "clones", 
      "activity", 
      "peptides", 
      "insulin", 
      "p21ras", 
      "cotransfectants", 
      "stimulation", 
      "basal", 
      "phosphorylation", 
      "microinjection", 
      "proliferation", 
      "vivo", 
      "GVBD", 
      "potency", 
      "induction", 
      "oocytes", 
      "insertion", 
      "fibroblasts", 
      "lysates", 
      "saturation density", 
      "maturation", 
      "assays", 
      "measurable rate", 
      "ISF", 
      "high activity", 
      "high ability", 
      "localization", 
      "region", 
      "complexes", 
      "stretch", 
      "differences", 
      "levels", 
      "domain", 
      "rate", 
      "presence", 
      "concentration", 
      "ability", 
      "proximity", 
      "conditions", 
      "ratio", 
      "time", 
      "conjunction", 
      "results", 
      "counterparts", 
      "medium", 
      "amount", 
      "transformation", 
      "density", 
      "GDP", 
      "stability", 
      "one"
    ], 
    "name": "Isoform-specific insertion near the Grb2-binding domain modulates the intrinsic guanine nucleotide exchange activity of hSos1", 
    "pagination": "1651-1661", 
    "productId": [
      {
        "name": "dimensions_id", 
        "type": "PropertyValue", 
        "value": [
          "pub.1020619112"
        ]
      }, 
      {
        "name": "doi", 
        "type": "PropertyValue", 
        "value": [
          "10.1038/sj.onc.1202483"
        ]
      }, 
      {
        "name": "pubmed_id", 
        "type": "PropertyValue", 
        "value": [
          "10208427"
        ]
      }
    ], 
    "sameAs": [
      "https://doi.org/10.1038/sj.onc.1202483", 
      "https://app.dimensions.ai/details/publication/pub.1020619112"
    ], 
    "sdDataset": "articles", 
    "sdDatePublished": "2022-09-02T15:48", 
    "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_315.jsonl", 
    "type": "ScholarlyArticle", 
    "url": "https://doi.org/10.1038/sj.onc.1202483"
  }
]
 

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.1202483'

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.1202483'

Turtle is a human-readable linked data format.

curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1038/sj.onc.1202483'

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.1202483'


 

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

321 TRIPLES      21 PREDICATES      133 URIs      116 LITERALS      24 BLANK NODES

Subject Predicate Object
1 sg:pub.10.1038/sj.onc.1202483 schema:about N0be0506de24d4c1cbfcea47528e2ad95
2 N13e1a1ca5d394ede88db34e0bb7fcaf1
3 N1c2eab9b4b214e2d9881c3ed6cb86fdd
4 N208f15519b1d438c9393a70b233edab5
5 N2baa002529044095b8471e2d0f558ec6
6 N45d9be8ce0d941879857eee4082d26cf
7 N52e518b4f3b54ca596fa7d824a16ff7f
8 N85a07e67e60042b8b9ff8bf01ec828e2
9 N94712263671b4d70ae9bb93e30d4a219
10 N94df973a888b4d27887e24cfc185d03e
11 Na3cacbe87d0b41b5b2e1c67401d9fb03
12 Na6cb798b4c284e03a03c42c56ee820ab
13 Nb1feaed0134c4e9baff69686b6512910
14 Nc93988d6e0e74ab49e242f1a635ebb02
15 Ncceb984fd6284312af4c2a8b411779db
16 Nd4a13ab59cdd4b17bd1dbceea81251b2
17 Nfd6da8eeccb14bb5b821d5000b82e787
18 anzsrc-for:11
19 anzsrc-for:1103
20 anzsrc-for:1112
21 schema:author N2d35ae06783448ae86b49030c5409367
22 schema:citation sg:pub.10.1007/bf03188808
23 sg:pub.10.1038/363015a0
24 sg:pub.10.1038/363045a0
25 sg:pub.10.1038/363083a0
26 sg:pub.10.1038/363085a0
27 sg:pub.10.1038/365781a0
28 sg:pub.10.1038/366643a0
29 sg:pub.10.1038/ng0795-294
30 schema:datePublished 1999-03-04
31 schema:datePublishedReg 1999-03-04
32 schema:description Two human hSos1 isoforms (Isf I and Isf II; Rojas et al., Oncogene 12, 2291 – 2300, 1996) defined by the presence of a distinct 15 amino acid stretch in one of them, were compared biologically and biochemically using representative NIH3T3 transfectants overexpressing either one. We showed that hSos1-Isf II is significantly more effective than hSos1-Isf I to induce proliferation or malignant transformation of rodent fibroblasts when transfected alone or in conjunction with normal H-Ras (Gly12). The hSos1-Isf II-Ras cotransfectants consistently exhibited higher saturation density, lower cell-doubling times, increased focus-forming activity and higher ability to grow on semisolid medium and at low serum concentration than their hSos1-Isf I-Ras counterparts. Furthermore, the ratio of GTP/GDP bound to cellular p21ras was consistently higher in the hSos1-Isf II-transfected clones, both under basal and stimulated conditions. However, no significant differences were detected in vivo between Isf I- and Isf II-transfected clones regarding the amount, stability and subcellular localization of Sos1-Grb2 complex, or the level of hSos1 phosphorylation upon cellular stimulation. Interestingly, direct Ras guanine nucleotide exchange activity assays in cellular lysates showed that Isf II transfectants consistently exhibited about threefold higher activity than Isf I transfectants under basal, unstimulated conditions. Microinjection into Xenopus oocytes of purified peptides corresponding to the C-terminal region of both isoforms (encompassing the 15 amino acid insertion area and the first Grb2-binding motif) showed that only the Isf II peptide, but not its corresponding Isf I peptide, was able to induce measurable rates of meiotic maturation, and synergyzed with insulin, but not progesterone, in induction of GVBD. Our results suggest that the increased biological potency displayed by hSos1-Isf II is due to higher intrinsic guanine nucleotide exchange activity conferred upon this isoform by the 15 a.a. insertion located in proximity to its Grb2 binding region.
33 schema:genre article
34 schema:isAccessibleForFree false
35 schema:isPartOf N79cba5408ea4427aa81664c23d8b98cd
36 Nd69d06733be849ab83dc461c71554976
37 sg:journal.1097543
38 schema:keywords C-terminal region
39 GDP
40 GTP/GDP
41 GVBD
42 Grb2
43 H-Ras
44 ISF
45 NIH3T3 transfectants
46 Ras guanine
47 Xenopus oocytes
48 ability
49 activity
50 activity assays
51 amino acid stretch
52 amount
53 assays
54 basal
55 biological potency
56 cell-doubling time
57 cellular lysates
58 cellular stimulation
59 clones
60 complexes
61 concentration
62 conditions
63 conjunction
64 cotransfectants
65 counterparts
66 density
67 differences
68 domain
69 exchange activity
70 fibroblasts
71 focus-forming activity
72 guanine
73 high ability
74 high activity
75 higher saturation density
76 induction
77 induction of GVBD
78 insertion
79 insulin
80 intrinsic guanine
81 isoforms
82 levels
83 localization
84 low serum concentrations
85 lysates
86 malignant transformation
87 maturation
88 measurable rate
89 medium
90 meiotic maturation
91 microinjection
92 normal H-ras
93 one
94 oocytes
95 p21ras
96 peptides
97 phosphorylation
98 potency
99 presence
100 proliferation
101 proximity
102 rate
103 ratio
104 region
105 results
106 rodent fibroblasts
107 saturation density
108 semisolid medium
109 serum concentrations
110 significant differences
111 stability
112 stimulation
113 stretch
114 subcellular localization
115 time
116 transfectants
117 transformation
118 unstimulated conditions
119 vivo
120 schema:name Isoform-specific insertion near the Grb2-binding domain modulates the intrinsic guanine nucleotide exchange activity of hSos1
121 schema:pagination 1651-1661
122 schema:productId N171644bee49a4bbf9611f5cb0f9c946a
123 N48df80704382440d9d272a30f6bfa097
124 Nc05a819a5f9e4119bfd463b056bc946a
125 schema:sameAs https://app.dimensions.ai/details/publication/pub.1020619112
126 https://doi.org/10.1038/sj.onc.1202483
127 schema:sdDatePublished 2022-09-02T15:48
128 schema:sdLicense https://scigraph.springernature.com/explorer/license/
129 schema:sdPublisher N539b185202dc4a2c88c4e6df298aef89
130 schema:url https://doi.org/10.1038/sj.onc.1202483
131 sgo:license sg:explorer/license/
132 sgo:sdDataset articles
133 rdf:type schema:ScholarlyArticle
134 N0be0506de24d4c1cbfcea47528e2ad95 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
135 schema:name Humans
136 rdf:type schema:DefinedTerm
137 N13e1a1ca5d394ede88db34e0bb7fcaf1 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
138 schema:name Transformation, Genetic
139 rdf:type schema:DefinedTerm
140 N171644bee49a4bbf9611f5cb0f9c946a schema:name doi
141 schema:value 10.1038/sj.onc.1202483
142 rdf:type schema:PropertyValue
143 N17851068f2464fee98c58e826c9641ce rdf:first sg:person.01310602233.41
144 rdf:rest N529d39d18f274ba8b8dc8bc4458f8022
145 N18c64d401fb84867a4f3e6ef092fdff0 rdf:first sg:person.01065110724.36
146 rdf:rest rdf:nil
147 N1c2eab9b4b214e2d9881c3ed6cb86fdd schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
148 schema:name Amino Acid Sequence
149 rdf:type schema:DefinedTerm
150 N208f15519b1d438c9393a70b233edab5 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
151 schema:name Mutagenesis, Insertional
152 rdf:type schema:DefinedTerm
153 N213a8d017f164c86b580215f279c7736 rdf:first sg:person.013055461504.59
154 rdf:rest N17851068f2464fee98c58e826c9641ce
155 N2895c84cfccb4a79acc6155f238de7d2 rdf:first sg:person.0617471620.87
156 rdf:rest Nb8bd9fcb5ec14dc3acabdfd4e8ca1834
157 N2baa002529044095b8471e2d0f558ec6 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
158 schema:name Animals
159 rdf:type schema:DefinedTerm
160 N2d35ae06783448ae86b49030c5409367 rdf:first sg:person.013461756342.19
161 rdf:rest N944fab801dbe43d7b6b5779d7490098f
162 N45d9be8ce0d941879857eee4082d26cf schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
163 schema:name ras Guanine Nucleotide Exchange Factors
164 rdf:type schema:DefinedTerm
165 N48df80704382440d9d272a30f6bfa097 schema:name dimensions_id
166 schema:value pub.1020619112
167 rdf:type schema:PropertyValue
168 N529d39d18f274ba8b8dc8bc4458f8022 rdf:first sg:person.0707261110.08
169 rdf:rest N2895c84cfccb4a79acc6155f238de7d2
170 N52e518b4f3b54ca596fa7d824a16ff7f schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
171 schema:name Molecular Sequence Data
172 rdf:type schema:DefinedTerm
173 N539b185202dc4a2c88c4e6df298aef89 schema:name Springer Nature - SN SciGraph project
174 rdf:type schema:Organization
175 N6182045fa9d84c78a09c609f67c5fa8a schema:affiliation grid-institutes:grid.48336.3a
176 schema:familyName Saez
177 schema:givenName Rosana
178 rdf:type schema:Person
179 N79cba5408ea4427aa81664c23d8b98cd schema:issueNumber 9
180 rdf:type schema:PublicationIssue
181 N85a07e67e60042b8b9ff8bf01ec828e2 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
182 schema:name Mice
183 rdf:type schema:DefinedTerm
184 N944fab801dbe43d7b6b5779d7490098f rdf:first sg:person.01226126661.04
185 rdf:rest Nd3cfe0deb6674b52b491696236cd48ed
186 N94712263671b4d70ae9bb93e30d4a219 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
187 schema:name GRB2 Adaptor Protein
188 rdf:type schema:DefinedTerm
189 N94df973a888b4d27887e24cfc185d03e schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
190 schema:name Proteins
191 rdf:type schema:DefinedTerm
192 Na3cacbe87d0b41b5b2e1c67401d9fb03 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
193 schema:name 3T3 Cells
194 rdf:type schema:DefinedTerm
195 Na6cb798b4c284e03a03c42c56ee820ab schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
196 schema:name Transfection
197 rdf:type schema:DefinedTerm
198 Nb1feaed0134c4e9baff69686b6512910 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
199 schema:name ras Proteins
200 rdf:type schema:DefinedTerm
201 Nb2394dd4115242e29e60cc8f0dc6faf5 rdf:first sg:person.01311724624.43
202 rdf:rest Nf87229b9b40841a3a3cab593543ace2b
203 Nb8bd9fcb5ec14dc3acabdfd4e8ca1834 rdf:first Ncacc34bf133e46b08062905c1297fb49
204 rdf:rest N18c64d401fb84867a4f3e6ef092fdff0
205 Nc05a819a5f9e4119bfd463b056bc946a schema:name pubmed_id
206 schema:value 10208427
207 rdf:type schema:PropertyValue
208 Nc93988d6e0e74ab49e242f1a635ebb02 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
209 schema:name Binding Sites
210 rdf:type schema:DefinedTerm
211 Ncacc34bf133e46b08062905c1297fb49 schema:affiliation grid-institutes:grid.418021.e
212 schema:familyName Kamata
213 schema:givenName Toru
214 rdf:type schema:Person
215 Ncceb984fd6284312af4c2a8b411779db schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
216 schema:name Protein Isoforms
217 rdf:type schema:DefinedTerm
218 Nd3cfe0deb6674b52b491696236cd48ed rdf:first sg:person.01243611424.29
219 rdf:rest Nb2394dd4115242e29e60cc8f0dc6faf5
220 Nd4a13ab59cdd4b17bd1dbceea81251b2 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
221 schema:name Guanine Nucleotide Exchange Factors
222 rdf:type schema:DefinedTerm
223 Nd69d06733be849ab83dc461c71554976 schema:volumeNumber 18
224 rdf:type schema:PublicationVolume
225 Nf87229b9b40841a3a3cab593543ace2b rdf:first N6182045fa9d84c78a09c609f67c5fa8a
226 rdf:rest N213a8d017f164c86b580215f279c7736
227 Nfd6da8eeccb14bb5b821d5000b82e787 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
228 schema:name Adaptor Proteins, Signal Transducing
229 rdf:type schema:DefinedTerm
230 anzsrc-for:11 schema:inDefinedTermSet anzsrc-for:
231 schema:name Medical and Health Sciences
232 rdf:type schema:DefinedTerm
233 anzsrc-for:1103 schema:inDefinedTermSet anzsrc-for:
234 schema:name Clinical Sciences
235 rdf:type schema:DefinedTerm
236 anzsrc-for:1112 schema:inDefinedTermSet anzsrc-for:
237 schema:name Oncology and Carcinogenesis
238 rdf:type schema:DefinedTerm
239 sg:journal.1097543 schema:issn 0950-9232
240 1476-5594
241 schema:name Oncogene
242 schema:publisher Springer Nature
243 rdf:type schema:Periodical
244 sg:person.01065110724.36 schema:affiliation grid-institutes:grid.48336.3a
245 schema:familyName Santos
246 schema:givenName Eugenio
247 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01065110724.36
248 rdf:type schema:Person
249 sg:person.01226126661.04 schema:affiliation grid-institutes:grid.418021.e
250 schema:familyName Subleski
251 schema:givenName Marianne
252 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01226126661.04
253 rdf:type schema:Person
254 sg:person.01243611424.29 schema:affiliation grid-institutes:grid.48336.3a
255 schema:familyName Coque
256 schema:givenName Juan JR
257 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01243611424.29
258 rdf:type schema:Person
259 sg:person.013055461504.59 schema:affiliation grid-institutes:grid.418021.e
260 schema:familyName Li
261 schema:givenName Bao-Qun
262 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.013055461504.59
263 rdf:type schema:Person
264 sg:person.01310602233.41 schema:affiliation grid-institutes:grid.48336.3a
265 schema:familyName Lopez
266 schema:givenName Eva
267 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01310602233.41
268 rdf:type schema:Person
269 sg:person.01311724624.43 schema:affiliation grid-institutes:grid.48336.3a
270 schema:familyName Guerrero
271 schema:givenName Carmen
272 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01311724624.43
273 rdf:type schema:Person
274 sg:person.013461756342.19 schema:affiliation grid-institutes:grid.413448.e
275 schema:familyName Rojas
276 schema:givenName Jose M
277 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.013461756342.19
278 rdf:type schema:Person
279 sg:person.0617471620.87 schema:affiliation grid-institutes:grid.48336.3a
280 schema:familyName Aroca
281 schema:givenName Pilar
282 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0617471620.87
283 rdf:type schema:Person
284 sg:person.0707261110.08 schema:familyName Zarich
285 schema:givenName Natasha
286 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0707261110.08
287 rdf:type schema:Person
288 sg:pub.10.1007/bf03188808 schema:sameAs https://app.dimensions.ai/details/publication/pub.1038450869
289 https://doi.org/10.1007/bf03188808
290 rdf:type schema:CreativeWork
291 sg:pub.10.1038/363015a0 schema:sameAs https://app.dimensions.ai/details/publication/pub.1023945033
292 https://doi.org/10.1038/363015a0
293 rdf:type schema:CreativeWork
294 sg:pub.10.1038/363045a0 schema:sameAs https://app.dimensions.ai/details/publication/pub.1051359913
295 https://doi.org/10.1038/363045a0
296 rdf:type schema:CreativeWork
297 sg:pub.10.1038/363083a0 schema:sameAs https://app.dimensions.ai/details/publication/pub.1022031225
298 https://doi.org/10.1038/363083a0
299 rdf:type schema:CreativeWork
300 sg:pub.10.1038/363085a0 schema:sameAs https://app.dimensions.ai/details/publication/pub.1011022170
301 https://doi.org/10.1038/363085a0
302 rdf:type schema:CreativeWork
303 sg:pub.10.1038/365781a0 schema:sameAs https://app.dimensions.ai/details/publication/pub.1020168730
304 https://doi.org/10.1038/365781a0
305 rdf:type schema:CreativeWork
306 sg:pub.10.1038/366643a0 schema:sameAs https://app.dimensions.ai/details/publication/pub.1005902014
307 https://doi.org/10.1038/366643a0
308 rdf:type schema:CreativeWork
309 sg:pub.10.1038/ng0795-294 schema:sameAs https://app.dimensions.ai/details/publication/pub.1001925125
310 https://doi.org/10.1038/ng0795-294
311 rdf:type schema:CreativeWork
312 grid-institutes:grid.413448.e schema:alternateName Unidad de Biologia Celular, Centro Nacional de Biologia Fundamental, Instituto de Salud Carlos III, 28220, Majadahonda, Madrid, Spain
313 schema:name Laboratory of Cellular and Molecular Biology, National Cancer Institute, National Institutes of Health, 20892, Bethesda, Maryland, USA
314 Unidad de Biologia Celular, Centro Nacional de Biologia Fundamental, Instituto de Salud Carlos III, 28220, Majadahonda, Madrid, Spain
315 rdf:type schema:Organization
316 grid-institutes:grid.418021.e schema:alternateName Laboratory of Biochemical Physiology, NCI-FCRDC, 21071, Frederick, Maryland, USA
317 schema:name Laboratory of Biochemical Physiology, NCI-FCRDC, 21071, Frederick, Maryland, USA
318 rdf:type schema:Organization
319 grid-institutes:grid.48336.3a schema:alternateName Laboratory of Cellular and Molecular Biology, National Cancer Institute, National Institutes of Health, 20892, Bethesda, Maryland, USA
320 schema:name Laboratory of Cellular and Molecular Biology, National Cancer Institute, National Institutes of Health, 20892, Bethesda, Maryland, USA
321 rdf:type schema:Organization
 




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


...