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 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. Here, we report for the first time that the early signaling events triggered by interleukin-17 involve tyrosine phosphorylation of several members of the JAK and STAT proteins in human U937 monocytic leukemia cells. Immunoprecipitation with specific antibodies followed by Western blot analysis with antiphosphotyrosine antibody has shown that in U937 cells, interleukin-17 induces time-dependent stimulation 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 phosphorylation of these proteins strongly suggests that the JAK/STAT signaling pathway may play a major role in transducing signals from interleukin-17 receptors to the nucleus.
Subramaniam
S V
SV
Department of Biochemistry, Meharry Medical College, Nashville, Tennessee 37208, USA.
Cooper
R S
RS
Adunyah
S E
SE
D015153:Blotting, Western; D004268:DNA-Binding Proteins / Q000378:metabolism*; D006801:Humans; D020381:Interleukin-17 / Q000494:pharmacology*; D053613:Janus Kinase 1; D053614:Janus Kinase 2; D053616:Janus Kinase 3; D010766:Phosphorylation / Q000187:drug effects; D019000:Phosphotyrosine / Q000378:metabolism; D011233:Precipitin Tests; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism; D011518:Proto-Oncogene Proteins; D018123:Receptors, Interleukin / Q000032:analysis; D053722:Receptors, Interleukin-17; D011994:Recombinant Proteins / Q000032:analysis; D050794:STAT1 Transcription Factor; D050795:STAT2 Transcription Factor; D050796:STAT3 Transcription Factor; D050797:STAT4 Transcription Factor; D015398:Signal Transduction / Q000187:drug effects*; D053634:TYK2 Kinase; D013997:Time Factors; D015534:Trans-Activators / Q000378:metabolism*; D020298:U937 Cells
D004268:DNA-Binding Proteins; C109985:IL17RA protein, human; D020381:Interleukin-17; D011506:Proteins; D011518:Proto-Oncogene Proteins; D018123:Receptors, Interleukin; D053722:Receptors, Interleukin-17; D011994:Recombinant Proteins; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D050795:STAT2 Transcription Factor; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D050797:STAT4 Transcription Factor; C494090:STAT4 protein, human; D015534:Trans-Activators; D019000:Phosphotyrosine; D011505:Protein-Tyrosine Kinases; C507904:JAK1 protein, human; C507924:JAK2 protein, human; C507933:JAK3 protein, human; D053613:Janus Kinase 1; D053614:Janus Kinase 2; D053616:Janus Kinase 3; D053634:TYK2 Kinase; C070139:TYK2 protein, human