Tumor Necrosis Factor (TNF- ) Activates Jak1/Stat3-Stat5B Signaling through TNFR-1 in Human B Cells

The biological actions of tumor necrosis factor (TNF) are mediated by two cell surface receptors, TNFR-1 and TNFR-2. These receptors do not display protein tyrosine kinase activity. Nevertheless, an early TNFinduced activation of specific tyrosine kinases has been reported as an important cue to the cellular response to this cytokine. Here we present evidence that TNFinduces the activation of the cytoplasmic Janus tyrosine kinases Jak1 and Tyk2 in both human healthy peripheral and lymphoma B cells. This event was accompanied by the recruitment of a specific set of latent cytosolic transcription factors, Stat3 and Stat5b. Furthermore, Jak1 coprecipitated with TNFR-1 after TNFtreatment. These data suggest that at least in human B cells this cytokine can exert its biological effects through the Jak-Stat signaling pathway and that such signals are initiated through an interaction between TNFR-1 and Jak