Interleukin-17 induces rapid tyrosine phosphorylation and activation of raf-1 kinase in human monocytic progenitor cell line U937

Interleukin-17 is a T cell derived pro-inflammatory cytokine exhibiting mul tiple biological activities in a variety of cells and believed to fine tune all general phases of hematopoietic response. However, the signaling mecha nism of this novel cytokine remains unknown. The purpose of this study was to determine whether Interleukin-17 induces tyrosine phosphorylation of pro teins and to find out whether the raf-1 kinase signaling pathway is involve d in mediating its signaling. Using immunoblotting and immunocomplex kinase assays, we report that the early signaling events triggered by rhIL-17 inv olves rapid tyrosine phosphorylation of several cellular proteins including raf-1 within 0.5 to 30 min. Optimal stimulation of tyrosine phosphorylatio n was observed with 0.5 to 1.0 ng/ml of Interleukin-17. Further, Interleuki n-17 stimulates rapid activation of raf-1 kinase. These findings provide th e first evidence that the mechanism of IL-17 signaling involves rapid tyros ine phosphorylation and activation of raf-1 serine/threonine kinase. (C) 19 99 Academic Press.