{
    "title": "Tyrosine phosphorylation of Vav stimulates IL-6 production in mast cells by a Rac/c-Jun N-terminal kinase-dependent pathway.",
    "journal": "Journal of immunology (Baltimore, Md. : 1950)",
    "date": "1999",
    "authors": "Song JS, Haleem-Smith H, Arudchandran R, Gomez J, Scott PM, Mill JF, Tan TH, Rivera J",
    "reference": {
        "type": "PubMed",
        "id": "10395673",
        "url": "https://pubmed.ncbi.nlm.nih.gov/10395673"
    },
    "referenced_proteins": [
        "Q15759-1",
        "P05106-1",
        "Q9NP31-1",
        "P01763-1",
        "P06756-1",
        "Q8IZP0-1",
        "P01112-1",
        "P01593-1",
        "Q15080-1",
        "P19174-1",
        "Q92556-1",
        "P98077-1",
        "P01742-1",
        "Q13094-1",
        "P01782-1",
        "Q96JJ3-1",
        "P80748-1",
        "A2NJV5-1",
        "P54100-1",
        "A0A075B6S6-1",
        "P22694-1",
        "P01854-1",
        "P01714-1",
        "P01814-1",
        "P61586-1",
        "P06315-1",
        "Q16644-1",
        "P01721-1",
        "P04211-1",
        "O15264-1",
        "P45983-1",
        "P01780-1",
        "O00459-1",
        "P01700-1",
        "Q7L576-1",
        "P12319-1",
        "P01699-1",
        "Q96F07-1",
        "P0DOY3-1",
        "P01602-1",
        "P01597-1",
        "P04430-1",
        "P30273-1",
        "P01619-1",
        "P45985-1",
        "O75791-1",
        "A0A075B6P5-1",
        "P01767-1",
        "P01614-1",
        "P01100-1",
        "P07900-1",
        "Q15464-1",
        "P0CF74-1",
        "P42338-1",
        "P01706-1",
        "P06241-1",
        "P04792-1",
        "P01768-1",
        "P04432-1",
        "P63261-1",
        "Q13464-1",
        "P01825-1",
        "P16333-1",
        "P53778-1",
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        "P55160-1",
        "P01624-1",
        "P01817-1",
        "P01717-1",
        "Q14289-1",
        "P28482-1",
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    "referenced_glycans": [],
    "species": [
        {
            "name": "Homo sapiens",
            "taxid": 9606,
            "evidence": [
                {
                    "database": "UniProtKB",
                    "id": "Q15759",
                    "url": "https://www.uniprot.org/uniprot/Q15759"
                }
            ],
            "common_name": "Human"
        }
    ],
    "record_id": "pubmed.10395673",
    "abstract": "This study investigates whether the guanine nucleotide exchange activity of Vav is linked to cytokine production in mast cells. Overexpression of Vav in the RBL-2H3 mast cell line resulted in the constitutive tyrosine phosphorylation and activation of Vav. We analyzed the functional effect of Vav overexpression on cytokine production. IL-2 and IL-6 mRNA levels were dramatically increased in Vav-overexpressing cells and correlated with increased NF-AT activity. Little or no effect was observed on the mRNA levels of IL-3, IL-4, GM-CSF, TNF-alpha, and TGF-beta. FcepsilonRI engagement did not further enhance IL-2 and IL-6 mRNA levels and only slightly enhanced NF-AT activity, but dramatically increased the mRNA levels of other tested cytokines. To understand the signal transduction required, we focused primarily on IL-6 induction by measuring mitogen-activated protein kinase activity and analyzing the effects of mutant or dominant negative forms of Vav, Rac1, and c-Jun N-terminal kinase-1 (JNK1). Vav overexpression resulted in the constitutive activation of JNK1 with little or no effect on p38 mitogen-activated protein kinase and ERK2. This was dependent on Vav-mediated activation of Rac1 as a Dbl domain-mutated Vav, inactive Rac N17, and inactive JNK1 down-regulated the Vav-induced JNK1 or IL-6 responses. Vav expression, but not expression of domain-mutated Vav, increased IL-6 secretion from nonimmortalized bone marrow-derived mast cells upon FcepsilonRI engagement. We conclude that Vav phosphorylation contributes to IL-6 induction in mast cells.",
    "glycosylation": [],
    "mutagenesis": [],
    "snv": [],
    "phosphorylation": [],
    "glycation": []
}