Abstract

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.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA091839-04
Application #
6771044
Study Section
Hematology Subcommittee 2 (HEM)
Program Officer
Mufson, R Allan
Project Start
2001-07-01
Project End
2006-06-30
Budget Start
2004-07-01
Budget End
2005-06-30
Support Year
4
Fiscal Year
2004
Total Cost
$217,044
Indirect Cost

  Institution

Name
Virginia Commonwealth University
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
105300446
City
Richmond
State
VA
Country
United States
Zip Code
23298

  Publications

Kashyap, Mohit; Thornton, Angela M; Norton, Sarah Kennedy et al. (2008) Cutting edge: CD4 T cell-mast cell interactions alter IgE receptor expression and signaling. J Immunol 180:2039-43
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
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
Mann-Chandler, Meredith N; Kashyap, Mohit; Wright, Harry V et al. (2005) IFN-gamma induces apoptosis in developing mast cells. J Immunol 175:3000-5
Engler, Kristie L; Rudd, Meghan L; Ryan, John J et al. (2005) Autocrine actions of macrophage-derived catecholamines on interleukin-1 beta. J Neuroimmunol 160:87-91

Showing the most recent 10 out of 20 publications