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 multiple biological activities in a variety of cells and believed to fine tune all general phases of hematopoietic response. However, the signaling mechanism of this novel cytokine remains unknown. The purpose of this study was to determine whether Interleukin-17 induces tyrosine phosphorylation of proteins and to find out whether the raf-1 kinase signaling pathway is involved in mediating its signaling. Using immunoblotting and immunocomplex kinase assays, we report that the early signaling events triggered by rhIL-17 involves rapid tyrosine phosphorylation of several cellular proteins including raf-1 within 0.5 to 30 min. Optimal stimulation of tyrosine phosphorylation was observed with 0.5 to 1.0 ng/ml of Interleukin-17. Further, Interleukin-17 stimulates rapid activation of raf-1 kinase. These findings provide the first evidence that the mechanism of IL-17 signaling involves rapid tyrosine phosphorylation and activation of raf-1 serine/threonine kinase.
Subramaniam
S V
SV
Department of Biochemistry and Comprehensive Sickle Cell Center, Meharry Medical College, Nashville, Tennessee, 37208, USA.
Pearson
L L
LL
Adunyah
S E
SE
D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D020381:Interleukin-17 / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000187:drug effects; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000032:analysis; D019908:Proto-Oncogene Proteins c-raf / Q000378:metabolism*; D011994:Recombinant Proteins; D015398:Signal Transduction / Q000187:drug effects; D014443:Tyrosine / Q000378:metabolism*; D020298:U937 Cells / Q000187:drug effects*
D020381:Interleukin-17; D011994:Recombinant Proteins; D019000:Phosphotyrosine; D014443:Tyrosine; D019908:Proto-Oncogene Proteins c-raf