Stat5 is a transcriptional activator and repressor utilized by many cytokine receptors. Our data indicate that Stat5 is a critical component of IL-3- and SCF-mediated cell survival, proliferation, and cytokine production. The current proposal will elaborate the molecular mechanisms by which Stat5 controls these processes. Gain-of-function mutations in the SCF receptor, c-kit, are known to contribute to neoplasia, and correlate with a failure to undergo cytokine-induced apoptosis. We hypothesize that these features can be explained at least partly by constitutive Stat5 activation. This proposal will assess the contribution of Stat5 to cytokine-mediated cell survival, proliferation, cytokine production, and neoplastic transformation. As such, the resulting data will be important to the understanding and treatment of cancer.
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| Bailey, Daniel P; Kashyap, Mohit; Bouton, L Andrew et al. (2006) Interleukin-10 induces apoptosis in developing mast cells and macrophages. J Leukoc Biol 80:581-9 |
| Wright, Harry V; Bailey, Daniel; Kashyap, Mohit et al. (2006) IL-3-mediated TNF production is necessary for mast cell development. J Immunol 176:2114-21 |
| Harris, Amanda L; Ryan, John J; Farrell, Nicholas (2006) Biological consequences of trinuclear platinum complexes: comparison of [[trans-PtCl(NH3)2]2mu-(trans-Pt(NH3)2(H2N(CH2)6-NH2)2)]4+ (BBR 3464) with its noncovalent congeners. Mol Pharmacol 69:666-72 |
| Barnstein, Brian O; Li, Geqiang; Wang, Zhengqi et al. (2006) Stat5 expression is required for IgE-mediated mast cell function. J Immunol 177:3421-6 |
| Norozian, Farnaz; Kashyap, Mohit; Ramirez, Carlos D et al. (2006) TGFbeta1 induces mast cell apoptosis. Exp Hematol 34:579-87 |
| Kashyap, Mohit; Bailey, Daniel P; Gomez, Gregorio et al. (2005) TGF-beta1 inhibits late-stage mast cell maturation. Exp Hematol 33:1281-91 |
| Gomez, Gregorio; Ramirez, Carlos D; Rivera, Juan et al. (2005) TGF-beta 1 inhibits mast cell Fc epsilon RI expression. J Immunol 174:5987-93 |
| Huang, Zan; Coleman, John M; Su, Yan et al. (2005) SHP-1 regulates STAT6 phosphorylation and IL-4-mediated function in a cell type-specific manner. Cytokine 29:118-24 |
| Gomez, Gregorio; Gonzalez-Espinosa, Claudia; Odom, Sandra et al. (2005) Impaired FcepsilonRI-dependent gene expression and defective eicosanoid and cytokine production as a consequence of Fyn deficiency in mast cells. J Immunol 175:7602-10 |
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