{
  "abstract": "IQGAP1 (IQ motif-containing GTPase activating protein 1), a scaffold protein with >250 interacting partners, regulates several intracellular signaling cascades, thereby modulating cell functions. Post-translational modifications of IQGAP1 by ubiquitination or phosphorylation have been shown to alter its interactions with selected proteins. We previously demonstrated that phosphorylation of Tyr-1510 of IQGAP1 by the MET receptor tyrosine kinase creates a docking site for Src homology 2 (SH2) domains of Abl. The vascular endothelial growth factor receptor 2 (VEGFR2) orchestrates angiogenesis by promoting endothelial cell survival, proliferation, and migration. Here, we show that the VEGFR2 kinase stimulates tyrosine phosphorylation of IQGAP1 in vitro and in cells; the latter is independent of SRC. Analysis by LC-MS/MS identifies Tyr-855 as the predominant site of IQGAP1 phosphorylation. Using a microarray screen, we identified that the SH2 domains of seven proteins bind to a peptide containing Tyr-855 of IQGAP1 in a phosphorylation-dependent manner. To assess the functional effects of Tyr-855 phosphorylation, we replaced Tyr-855 of IQGAP1 with alanine (IQGAP1 Y855A). The ability of VEGF to activate Akt and ERK and increase cell proliferation is abrogated when IQGAP1-null cells are reconstituted with IQGAP1 Y855A, indicating that phosphorylation of Tyr-855 of IQGAP1 modulates the ability of VEGF to activate at least some signaling pathways and promote cell proliferation. Taken together, our data suggest that IQGAP1 phosphorylation is a potential therapeutic target for neoplasms and other disorders characterized by increased VEGFR2 signaling.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Laboratory Medicine, National Institutes of Health, Bethesda, Maryland, USA",
    "Discovery Analytical, GlaxoSmithKline, Collegeville, Pennsylvania, USA"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 7,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Mohammed Rizwan Babu Sait"
    },
    {
      "affs": [
        0
      ],
      "name": "Zhigang Li"
    },
    {
      "affs": [
        0
      ],
      "name": "Louise Thines"
    },
    {
      "affs": [
        1
      ],
      "name": "Tao Wang"
    },
    {
      "affs": [
        1
      ],
      "name": "Francesca Zappacosta"
    },
    {
      "affs": [
        1
      ],
      "name": "Roland S. Annan"
    },
    {
      "affs": [
        0
      ],
      "name": "David B. Sacks"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/2k1we2vxprjf3.bib",
  "cited_by": 0,
  "doi": "10.1016/j.jbc.2026.113593",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13717184/",
  "id": "2k1we2vxprjf3",
  "issns": [
    "0021-9258",
    "1083-351X"
  ],
  "landing_url": "https://doi.org/10.1016/j.jbc.2026.113593",
  "language": "en",
  "licence": "CC-BY-NC-ND-4.0",
  "licence_label": "CC BY-NC-ND 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Research Article"
    ],
    [
      "openalex",
      "1312|Angiogenesis and VEGF in Cancer"
    ]
  ],
  "openalex": "W7214063306",
  "pdf_url": null,
  "pmcid": "PMC13717184",
  "pmid": "42772568",
  "published": "2026-09-23",
  "publisher": "American Society for Biochemistry and Molecular Biology",
  "ris": "https://research.draconitic.com/paper/2k1we2vxprjf3.ris",
  "sources": [
    {
      "first_seen": "2026-11-02T12:21:33Z",
      "native_id": "PMC13717184",
      "source": "pmc",
      "url": "https://doi.org/10.1016/j.jbc.2026.113593"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Angiogenesis and VEGF in Cancer",
      "subfield": "molecular-biology"
    }
  ],
  "title": "Tyrosine phosphorylation of the scaffold protein IQGAP1 by VEGFR2 modulates cell proliferation",
  "title_text": "Tyrosine phosphorylation of the scaffold protein IQGAP1 by VEGFR2 modulates cell proliferation",
  "type": "peer-reviewed",
  "updated_at": "2026-11-02T12:21:33Z",
  "url": "https://research.draconitic.com/paper/2k1we2vxprjf3",
  "venue": "The Journal of Biological Chemistry",
  "versions": []
}