ag-490 and HTLV-I-Infections

Examination of signaling pathways used by HTLV-1-infected rabbit cell lines revealed differences between one, RH/K30, that mediates asymptomatic infection and another, RH/K34, that causes lethal experimental leukemia. Both lines are IL-2 independent; RH/K30 produces IL-4 while RH/K34 produces IL-10. Examination of the Jak/STAT (Janus kinase/signal transducer and activator of transcription) activation of the lines revealed constitutive phosphorylation of Jak1 in both STAT6 phosphorylation, not previously reported for HTLV-1 cells, was observed in RH/K30; STAT1 and STAT3 were phosphorylated in RH/K34. Treatment with cytokines altered the activation of the STAT proteins: IL-2 induced STAT5 phosphorylation in both lines. Supernatant from RH/K34 or IL-10 induced STAT3 phosphorylation in RH/K30 cells. Supernatant from RH/K30 or IL-4 induced STAT6 phosphorylation in RH/K34 cells, which could be reversed with a Jak kinase inhibitor--AG-490.

Topics: Animals; Cell Line; Disease Models, Animal; DNA-Binding Proteins; Enzyme Inhibitors; Gene Expression; HTLV-I Infections; Human T-lymphotropic virus 1; Humans; Interleukin-10; Interleukin-2; Interleukin-4; Janus Kinase 1; Milk Proteins; Phosphorylation; Protein-Tyrosine Kinases; Rabbits; Signal Transduction; STAT1 Transcription Factor; STAT3 Transcription Factor; STAT5 Transcription Factor; STAT6 Transcription Factor; Trans-Activators; Tumor Cells, Cultured; Tyrphostins