Scientific Report 2003-2004 - Cleveland Clinic Lerner Research ...

THE LARNERLABORATORYPOSTDOCTORAL FELLOWMaria Navarro, Ph.D.The Department of ImmunologySignaling Cascades that Regulate theBiological Actions of InterferonsGRADUATE STUDENTSRamesh PotlaJinzhong QinMy laboratory is interested in the signalingcascades regulated by interferons and howthese various cascades are responsible forthe biological actions of these cytokines. There arethree main efforts ongoing in the laboratory.One project examines the role of tyrosinekinases and phosphatases that have traditionallybeen associated with signaling through the T-cellreceptor in the antiproliferative actions ofinterferons. Another project examines themechanisms by which interferons stimulateprogrammed cell death. The third project, justinitiated, will examine the signaling cascadesrequired for interferons to downregulate cellularRNAs both transcriptionally andposttranscriptionally.Andrew C. Larner, M.D., Ph.D.Petricoin, E.F. III, Ito, S., Williams, B.L., Audet, S., Stancato, L.F., Gamero, A., Clouse, K., Grimley, P.,Weiss, A., Beeler, J., Finbloom, D.S., Shores, E.W., Abraham, R., and A.C. Larner (1997) Antiproliferativeaction of IFN-alpha requires components of T-cell receptor signaling. Nature 390:629-632.Stancato, L.F., Yu, C.-R., Petricoin, E.F., and A.C. Larner (1998) Activation of Raf-1 by interferon-gammaand oncostatin M requires expression of the Stat1 transcription factor. J. Biol. Chem. 273:18701-18704.Gamero, A.M., and A.C. Larner (2000) Signaling via the T-cell antigen receptor induces phosphorylation ofStat1 on serine 727. J. Biol. Chem. 275:16574-16578.Larner, A.C., and A. Keightley (2000) The Jak/Stat signaling cascade: its role in the biological effects ofinterferons. In: Gudkind, J.S., ed. Signaling Networks and Cell Cycle Control: The Molecular Basis ofCancer and Other Diseases. Totowa, NJ: Humana Press, Inc., pp. 393-409.Dong F, Gutkind, S.J., and A.C. Larner (2001) Granulocyte colony-stimulating factor Induces Erk5 activationwhich is differentially regulated by protein tyrosine kinases and protein kinase C and is involved inthe regulation of cell proliferation and survival. J. Biol. Chem. 276:10811-10816.Gamero, A.M., and A,C. Larner (2001) Vanadate stimulates interferon-mediated apoptosis that is dependenton the Jak/Stat pathway. J. Biol. Chem. 276:13547-13553.94