Evidence for the involvement of JAK/STAT pathway in the signaling mechanism of interleukin-17

Interleukin-17 is a T-cell-derived pro-inflammatory cytokine, exhibiting mu ltiple biological activities in a variety of cells and believed to fine tun e all general phases of hematopoietic response. However, the signaling mech anism of this novel cytokine remains unknown. Here, we report for the first time that the early signaling events triggered by interleukin-17 involve t yrosine phosphorylation of several members of the JAK and STAT proteins in human U937 monocytic leukemia cells. Immunoprecipitation with specific anti bodies followed by Western blot analysis with antiphosphotyrosine antibody has shown that in U937 cells, interleukin-17 induces time-dependent stimula tion of tyrosine phosphorylation of JAK 1, 2 and 3, Tyk 2 and STAT 1, 2, 3 and 4 within 0.5 to 30 min. Interleukin-17-mediated tyrosine phosphorylatio n of these proteins strongly suggests that the JAK/STAT signaling pathway m ay play a major role in transducing signals from interleukin-17 receptors t o the nucleus. (C) 1999 Academic Press.