{
  "abstract": "Small GTPases of the Ras superfamily act as molecular switches cycling between GDP-bound inactive and GTP-bound active states. Their signaling output depends not only on GTP loading but on continuous nucleotide cycling controlled by guanine nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs). While Glycine 12 substitutions in Ras typically confer constitutive activation, the effects of equivalent mutations in Rho-family GTPases remain poorly defined. Here, we characterize a ClinVar-reported RhoGG12E variant. Quantitative kinetic studies show that RhoGG12E has strongly impaired intrinsic and GAP-stimulated GTP hydrolysis but it can still be activated by GEFs. Effector binding is preserved in vitro and RhoGG12E accumulates in a GTP-bound state in cells. Yet, RhoGG12E induces enhanced spreading, increased focal adhesions, and reduced collective migration-phenotypes consistent with previously reported consequences of reduced RhoG signaling rather than hyperactivation. These findings indicate that accumulation of the GTP-bound form of small GTPases does not necessarily translate into productive output, supporting a model in which impaired nucleotide cycling compromises RhoG-dependent cellular behaviors.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": null,
  "arxiv": null,
  "author_total": 7,
  "authors": [
    {
      "name": "Shah Wajed"
    },
    {
      "name": "Yann Ferrandez"
    },
    {
      "name": "Mahel Zeghouf"
    },
    {
      "name": "Rasta Ghasemi"
    },
    {
      "name": "Cylia Puertas"
    },
    {
      "name": "Agata Nawrotek"
    },
    {
      "name": "Franck Gesbert"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/drfvrp047a53j.bib",
  "cited_by": 0,
  "doi": "10.1042/bcj20260225",
  "fulltext_url": null,
  "id": "drfvrp047a53j",
  "issns": [
    "0264-6021",
    "1470-8728"
  ],
  "landing_url": "https://hal.science/hal-05746792v1",
  "language": "en",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "hal",
      "0.sdv"
    ],
    [
      "openalex",
      "1312|Protein Kinase Regulation and GTPase Signaling"
    ]
  ],
  "openalex": "W7166875142",
  "pdf_url": null,
  "pmcid": null,
  "pmid": null,
  "published": "2026-08-05",
  "publisher": "Portland Press",
  "ris": "https://research.draconitic.com/paper/drfvrp047a53j.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:33Z",
      "native_id": "hal-05746792",
      "source": "hal",
      "url": "https://hal.science/hal-05746792v1"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Protein Kinase Regulation and GTPase Signaling",
      "subfield": "molecular-biology"
    }
  ],
  "title": "Persistence without turnover: the RhoG G12E mutant highlights the role of nucleotide cycling in RhoG signaling",
  "title_text": "Persistence without turnover: the RhoG G12E mutant highlights the role of nucleotide cycling in RhoG signaling",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:17:33Z",
  "url": "https://research.draconitic.com/paper/drfvrp047a53j",
  "venue": "Biochemical Journal",
  "versions": []
}