{
    "record_id": "pubmed.10395673", 
    "reference": {
        "url": "https://www.ncbi.nlm.nih.gov/pubmed/10395673", 
        "type": "PubMed", 
        "id": "10395673"
    }, 
    "title": "Tyrosine phosphorylation of Vav stimulates IL-6 production in mast cells by a Rac/c-Jun N-terminal kinase-dependent pathway.", 
    "mutagenesis": [], 
    "journal": "J. Immunol.", 
    "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": [], 
    "snv": [], 
    "referenced_glycans": [], 
    "phosphorylation": [], 
    "authors": "Gomez J., Rivera J., Song J.S., Tan T.-H., Arudchandran R., Haleem-Smith H., Mill J.F., Scott P.M.", 
    "date": "1999", 
    "referenced_proteins": [
        "P54100-1"
    ], 
    "species": [
        {
            "common_name": "Rat", 
            "taxid": 10116, 
            "name": "Rattus norvegicus", 
            "evidence": [
                {
                    "url": "https://www.uniprot.org/uniprot/P54100", 
                    "id": "P54100", 
                    "database": "UniProtKB"
                }
            ]
        }
    ], 
    "glycation": []
}